Publications

@article{jansz_endogenous_2021,

title = {Endogenous retroviruses in the origins and treatment of cancer},

author = {Natasha Jansz and Geoffrey J Faulkner},

url = {https://doi.org/10.1186/s13059-021-02357-4},

doi = {10.1186/s13059-021-02357-4},

issn = {1474-760X},

year  = {2021},

date = {2021-05-01},

urldate = {2021-08-09},

journal = {Genome Biology},

volume = {22},

number = {1},

pages = {147},

abstract = {Endogenous retroviruses (ERVs) are emerging as promising therapeutic targets in cancer. As remnants of ancient retroviral infections, ERV-derived regulatory elements coordinate expression from gene networks, including those underpinning embryogenesis and immune cell function. ERV activation can promote an interferon response, a phenomenon termed viral mimicry. Although ERV expression is associated with cancer, and provisionally with autoimmune and neurodegenerative diseases, ERV-mediated inflammation is being explored as a way to sensitize tumors to immunotherapy. Here we review ERV co-option in development and innate immunity, the aberrant contribution of ERVs to tumorigenesis, and the wider biomedical potential of therapies directed at ERVs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ewing_nanopore_2020,

title = {Nanopore Sequencing Enables Comprehensive Transposable Element Epigenomic Profiling},

author = {Adam D Ewing and Nathan Smits and Francisco J Sanchez-Luque and Jamila Faivre and Paul M Brennan and Sandra R Richardson and Seth W Cheetham and Geoffrey J Faulkner},

url = {http://www.sciencedirect.com/science/article/pii/S1097276520307310},

doi = {10.1016/j.molcel.2020.10.024},

issn = {1097-2765},

year  = {2020},

date = {2020-01-01},

urldate = {2020-11-30},

journal = {Molecular Cell},

abstract = {Transposable elements (TEs) drive genome evolution and are a notable source of pathogenesis, including cancer. While CpG methylation regulates TE activity, the locus-specific methylation landscape of mobile human TEs has to date proven largely inaccessible. Here, we apply new computational tools and long-read nanopore sequencing to directly infer CpG methylation of novel and extant TE insertions in hippocampus, heart, and liver, as well as paired tumor and non-tumor liver. As opposed to an indiscriminate stochastic process, we find pronounced demethylation of young long interspersed element 1 (LINE-1) retrotransposons in cancer, often distinct to the adjacent genome and other TEs. SINE-VNTR-Alu (SVA) retrotransposons, including their internal tandem repeat-associated CpG island, are near-universally methylated. We encounter allele-specific TE methylation and demethylation of aberrantly expressed young LINE-1s in normal tissues. Finally, we recover the complete sequences of tumor-specific LINE-1 insertions and their retrotransposition hallmarks, demonstrating how long-read sequencing can simultaneously survey the epigenome and detect somatic TE mobilization.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cheetham_overcoming_2020,

title = {Overcoming challenges and dogmas to understand the functions of pseudogenes},

author = {Seth W Cheetham and Geoffrey J Faulkner and Marcel E Dinger},

url = {https://www.nature.com/articles/s41576-019-0196-1},

doi = {10.1038/s41576-019-0196-1},

issn = {1471-0064},

year  = {2020},

date = {2020-01-01},

urldate = {2020-11-30},

journal = {Nature Reviews Genetics},

volume = {21},

number = {3},

pages = {191--201},

abstract = {Pseudogenes are defined as regions of the genome that contain defective copies of genes. They exist across almost all forms of life, and in mammalian genomes are annotated in similar numbers to recognized protein-coding genes. Although often presumed to lack function, growing numbers of pseudogenes are being found to play important biological roles. In consideration of their evolutionary origins and inherent limitations in genome annotation practices, we posit that pseudogenes have been classified on a scientifically unsubstantiated basis. We reflect that a broad misunderstanding of pseudogenes, perpetuated in part by the pejorative inference of the ‘pseudogene’ label, has led to their frequent dismissal from functional assessment and exclusion from genomic analyses. With the advent of technologies that simplify the study of pseudogenes, we propose that an objective reassessment of these genomic elements will reveal valuable insights into genome function and evolution.},

note = {Number: 3 

Publisher: Nature Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{salvador-palomeque_dynamic_2019,

title = {Dynamic Methylation of an L1 Transduction Family during Reprogramming and Neurodifferentiation},

author = {Carmen Salvador-Palomeque and Francisco J Sanchez-Luque and Patrick R J Fortuna and Adam D Ewing and Ernst J Wolvetang and Sandra R Richardson and Geoffrey J Faulkner},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425141/},

doi = {10.1128/MCB.00499-18},

issn = {0270-7306},

year  = {2019},

date = {2019-01-01},

urldate = {2019-06-07},

journal = {Mol Cell Biol},

volume = {39},

number = {7},

abstract = {The retrotransposon LINE-1 (L1) is a significant source of endogenous mutagenesis in humans. In each individual genome, a few retrotransposition-competent L1s (RC-L1s) can generate new heritable L1 insertions in the early embryo, primordial germ line, and germ cells., The retrotransposon LINE-1 (L1) is a significant source of endogenous mutagenesis in humans. In each individual genome, a few retrotransposition-competent L1s (RC-L1s) can generate new heritable L1 insertions in the early embryo, primordial germ line, and germ cells. L1 retrotransposition can also occur in the neuronal lineage and cause somatic mosaicism. Although DNA methylation mediates L1 promoter repression, the temporal pattern of methylation applied to individual RC-L1s during neurogenesis is unclear. Here, we identified a de novo L1 insertion in a human induced pluripotent stem cell (hiPSC) line via retrotransposon capture sequencing (RC-seq). The L1 insertion was full-length and carried 5ʹ and 3ʹ transductions. The corresponding donor RC-L1 was part of a large and recently active L1 transduction family and was highly mobile in a cultured-cell L1 retrotransposition reporter assay. Notably, we observed distinct and dynamic DNA methylation profiles for the de novo L1 and members of its extended transduction family during neuronal differentiation. These experiments reveal how a de novo L1 insertion in a pluripotent stem cell is rapidly recognized and repressed, albeit incompletely, by the host genome during neurodifferentiation, while retaining potential for further retrotransposition.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{sanchez-luque_line-1_2019,

title = {LINE-1 Evasion of Epigenetic Repression in Humans},

author = {Francisco J Sanchez-Luque and Marie-Jeanne H C Kempen and Patricia Gerdes and Dulce B Vargas-Landin and Sandra R Richardson and Robin-Lee Troskie and Samuel J Jesuadian and Seth W Cheetham and Patricia E Carreira and Carmen Salvador-Palomeque and Marta Garc\'{i}a-Ca\~{n}adas and Martin Mu\~{n}oz-Lopez and Laura Sanchez and Mischa Lundberg and Angela Macia and Sara R Heras and Paul M Brennan and Ryan Lister and Jose L Garcia-Perez and Adam D Ewing and Geoffrey J Faulkner},

url = {https://www.cell.com/molecular-cell/abstract/S1097-2765(19)30396-X},

doi = {10.1016/j.molcel.2019.05.024},

issn = {1097-2765},

year  = {2019},

date = {2019-01-01},

urldate = {2019-06-24},

journal = {Molecular Cell},

volume = {0},

number = {0},

abstract = {textlessh2textgreaterSummarytextless/h2textgreatertextlessptextgreaterEpigenetic silencing defends against LINE-1 (L1) retrotransposition in mammalian cells. However, the mechanisms that repress young L1 families and how L1 escapes to cause somatic genome mosaicism in the brain remain unclear. Here we report that a conserved Yin Yang 1 (YY1) transcription factor binding site mediates L1 promoter DNA methylation in pluripotent and differentiated cells. By analyzing 24 hippocampal neurons with three distinct single-cell genomic approaches, we characterized and validated a somatic L1 insertion bearing a 3ʹ transduction. The source (donor) L1 for this insertion was slightly 5ʹ truncated, lacked the YY1 binding site, and was highly mobile when tested textitin vitro. Locus-specific bisulfite sequencing revealed that the donor L1 and other young L1s with mutated YY1 binding sites were hypomethylated in embryonic stem cells, during neurodifferentiation, and in liver and brain tissue. These results explain how L1 can evade repression and retrotranspose in the human body.textless/ptextgreater},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{bodea_retrotransposon-induced_2018,

title = {Retrotransposon-induced mosaicism in the neural genome},

author = {Gabriela O Bodea and Eleanor G Z McKelvey and Geoffrey J Faulkner},

url = {http://rsob.royalsocietypublishing.org/content/8/7/180074},

doi = {10.1098/rsob.180074},

issn = {2046-2441},

year  = {2018},

date = {2018-07-01},

urldate = {2018-08-28},

journal = {Open Biology},

volume = {8},

number = {7},

pages = {180074},

abstract = {Over the past decade, major discoveries in retrotransposon biology have depicted the neural genome as a dynamic structure during life. In particular, the retrotransposon LINE-1 (L1) has been shown to be transcribed and mobilized in the brain. Retrotransposition in the developing brain, as well as during adult neurogenesis, provides a milieu in which neural diversity can arise. Dysregulation of retrotransposon activity may also contribute to neurological disease. Here, we review recent reports of retrotransposon activity in the brain, and discuss the temporal nature of retrotransposition and its regulation in neural cells in response to stimuli. We also put forward hypotheses regarding the significance of retrotransposons for brain development and neurological function, and consider the potential implications of this phenomenon for neuropsychiatric and neurodegenerative conditions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{richardson_heritable_2018,

title = {Heritable L1 Retrotransposition Events During Development: Understanding Their Origins},

author = {Sandra R Richardson and Geoffrey J Faulkner},

url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/bies.201700189},

doi = {10.1002/bies.201700189},

issn = {1521-1878},

year  = {2018},

date = {2018-06-01},

urldate = {2018-08-28},

journal = {BioEssays},

volume = {40},

number = {6},

pages = {1700189},

abstract = {The retrotransposon Long Interspersed Element 1 (LINE-1 or L1) has played a major role in shaping the sequence composition of the mammalian genome. In our recent publication, “Heritable L1 retrotransposition in the mouse primordial germline and early embryo,” we systematically assessed the rate and developmental timing of de novo, heritable endogenous L1 insertions in mice. Such heritable retrotransposition events allow L1 to exert an ongoing influence upon genome evolution. Here, we place our findings in the context of earlier studies, and highlight how our results corroborate, and depart from, previous research based on human patient samples and transgenic mouse models harboring engineered L1 reporter genes. In parallel, we outline outstanding questions regarding the stage-specificity, regulation, and functional impact of embryonic and germline L1 retrotransposition, and propose avenues for future research in this field.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nguyen_l1_2018,

title = {L1 Retrotransposon Heterogeneity in Ovarian Tumor Cell Evolution},

author = {Thu H M Nguyen and Patricia E Carreira and Francisco J Sanchez-Luque and Stephanie N Schauer and Allister C Fagg and Sandra R Richardson and Claire M Davies and Samuel J Jesuadian and Marie-Jeanne H C Kempen and Robin-Lee Troskie and Cini James and Elizabeth A Beaven and Tristan P Wallis and Jermaine I G Coward and Naven P Chetty and Alexander J Crandon and Deon J Venter and Jane E Armes and Lewis C Perrin and John D Hooper and Adam D Ewing and Kyle R Upton and Geoffrey J Faulkner},

url = {http://www.sciencedirect.com/science/article/pii/S2211124718308714},

doi = {10.1016/j.celrep.2018.05.090},

issn = {2211-1247},

year  = {2018},

date = {2018-06-01},

urldate = {2018-08-28},

journal = {Cell Reports},

volume = {23},

number = {13},

pages = {3730--3740},

abstract = {Summary 

LINE-1 (L1) retrotransposons are a source of insertional mutagenesis in tumor cells. However, the clinical significance of L1 mobilization during tumorigenesis remains unclear. Here, we applied retrotransposon capture sequencing (RC-seq) to multiple single-cell clones isolated from five ovarian cancer cell lines and HeLa cells and detected endogenous L1 retrotransposition in vitro. We then applied RC-seq to ovarian tumor and matched blood samples from 19 patients and identified 88 tumor-specific L1 insertions. In one tumor, an intronic de novo L1 insertion supplied a novel cis-enhancer to the putative chemoresistance gene STC1. Notably, the tumor subclone carrying the STC1 L1 mutation increased in prevalence after chemotherapy, further increasing STC1 expression. We also identified hypomethylated donor L1s responsible for new L1 insertions in tumors and cultivated cancer cells. These congruent in vitro and in vivo results highlight L1 insertional mutagenesis as a common component of ovarian tumorigenesis and cancer genome heterogeneity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{faulkner_l1_2018,

title = {L1 retrotransposition in the soma: a field jumping ahead},

author = {Geoffrey J Faulkner and Victor Billon},

url = {https://doi.org/10.1186/s13100-018-0128-1},

doi = {10.1186/s13100-018-0128-1},

issn = {1759-8753},

year  = {2018},

date = {2018-01-01},

urldate = {2018-08-28},

journal = {Mobile DNA},

volume = {9},

number = {1},

pages = {22},

abstract = {Retrotransposons are transposable elements (TEs) capable of “jumping” in germ, embryonic and tumor cells and, as is now clearly established, in the neuronal lineage. Mosaic TE insertions form part of a broader landscape of somatic genome variation and hold significant potential to generate phenotypic diversity, in the brain and elsewhere. At present, the LINE-1 (L1) retrotransposon family appears to be the most active autonomous TE in most mammals, based on experimental data obtained from disease-causing L1 mutations, engineered L1 reporter systems tested in cultured cells and transgenic rodents, and single-cell genomic analyses. However, the biological consequences of almost all somatic L1 insertions identified thus far remain unknown. In this review, we briefly summarize the current state-of-the-art in the field, including estimates of L1 retrotransposition rate in neurons. We bring forward the hypothesis that an extensive subset of retrotransposition-competent L1s may be de-repressed and mobile in the soma but largely inactive in the germline. We discuss recent reports of non-canonical L1-associated sequence variants in the brain and propose that the elevated L1 DNA content reported in several neurological disorders may predominantly comprise accumulated, unintegrated L1 nucleic acids, rather than somatic L1 insertions. Finally, we consider the main objectives and obstacles going forward in elucidating the biological impact of somatic retrotransposition.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{abrams_meeting_2018,

title = {Meeting report: mobile genetic elements and genome plasticity 2018},

author = {John M Abrams and Irina R Arkhipova and Marlene Belfort and Jef D Boeke and M Joan Curcio and Geoffrey J Faulkner and John L Goodier and Ruth Lehmann and Henry L Levin},

url = {https://doi.org/10.1186/s13100-018-0126-3},

doi = {10.1186/s13100-018-0126-3},

issn = {1759-8753},

year  = {2018},

date = {2018-01-01},

urldate = {2018-08-28},

journal = {Mobile DNA},

volume = {9},

number = {1},

pages = {21},

abstract = {The Mobile Genetic Elements and Genome Plasticity conference was hosted by Keystone Symposia in Santa Fe, NM USA, February 11\textendash15, 2018. The organizers were Marlene Belfort, Evan Eichler, Henry Levin and Lynn Maquat. The goal of this conference was to bring together scientists from around the world to discuss the function of transposable elements and their impact on host species. Central themes of the meeting included recent innovations in genome analysis and the role of mobile DNA in disease and evolution. The conference included 200 scientists who participated in poster presentations, short talks selected from abstracts, and invited talks. A total of 58 talks were organized into eight sessions and two workshops. The topics varied from mechanisms of mobilization, to the structure of genomes and their defense strategies to protect against transposable elements.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{baillie_shared_2018,

title = {Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease},

author = {Kenneth J Baillie and Andrew Bretherick and Christopher S Haley and Sara Clohisey and Alan Gray and Lucile P A Neyton and Jeffrey Barrett and Eli A Stahl and Albert Tenesa and Robin Andersson and Ben J Brown and Geoffrey J Faulkner and Marina Lizio and Ulf Schaefer and Carsten Daub and Masayoshi Itoh and Naoto Kondo and Timo Lassmann and Jun Kawai and Iibdgc Consortium and Damian Mole and Vladimir B Bajic and Peter Heutink and Michael Rehli and Hideya Kawaji and Albin Sandelin and Harukazu Suzuki and Jack Satsangi and Christine A Wells and Nir Hacohen and Thomas C Freeman and Yoshihide Hayashizaki and Piero Carninci and Alistair R R Forrest and David A Hume},

url = {http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005934},

doi = {10.1371/journal.pcbi.1005934},

issn = {1553-7358},

year  = {2018},

date = {2018-01-01},

urldate = {2018-08-28},

journal = {PLOS Computational Biology},

volume = {14},

number = {3},

pages = {e1005934},

abstract = {Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn’s disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{schauer_l1_2018,

title = {L1 retrotransposition is a common feature of mammalian hepatocarcinogenesis},

author = {Stephanie N Schauer and Patricia E Carreira and Ruchi Shukla and Daniel J Gerhardt and Patricia Gerdes and Francisco J Sanchez-Luque and Paola Nicoli and Michaela Kindlova and Serena Ghisletti and Alexandre Dos Santos and Delphine Rapoud and Didier Samuel and Jamila Faivre and Adam D Ewing and Sandra R Richardson and Geoffrey J Faulkner},

url = {http://genome.cshlp.org/content/early/2018/04/11/gr.226993.117},

doi = {10.1101/gr.226993.117},

issn = {1088-9051, 1549-5469},

year  = {2018},

date = {2018-01-01},

urldate = {2018-08-28},

journal = {Genome Research},

abstract = {The retrotransposon Long Interspersed Element 1 (LINE-1 or L1) is a continuing source of germline and somatic mutagenesis in mammals. Deregulated L1 activity is a hallmark of cancer, and L1 mutagenesis has been described in numerous human malignancies. We previously employed retrotransposon capture sequencing (RC-seq) to analyze hepatocellular carcinoma (HCC) samples from patients infected with hepatitis B or hepatitis C virus and identified L1 variants responsible for activating oncogenic pathways. Here, we have applied RC-seq and whole-genome sequencing (WGS) to an Abcb4 (Mdr2)−/− mouse model of hepatic carcinogenesis and demonstrated for the first time that L1 mobilization occurs in murine tumors. In 12 HCC nodules obtained from 10 animals, we validated four somatic L1 insertions by PCR and capillary sequencing, including TF subfamily elements, and one GF subfamily example. One of the TF insertions carried a 3′ transduction, allowing us to identify its donor L1 and to demonstrate that this full-length TF element retained retrotransposition capacity in cultured cancer cells. Using RC-seq, we also identified eight tumor-specific L1 insertions from 25 HCC patients with a history of alcohol abuse. Finally, we used RC-seq and WGS to identify three tumor-specific L1 insertions among 10 intra-hepatic cholangiocarcinoma (ICC) patients, including one insertion traced to a donor L1 on Chromosome 22 known to be highly active in other cancers. This study reveals L1 mobilization as a common feature of hepatocarcinogenesis in mammals, demonstrating that the phenomenon is not restricted to human viral HCC etiologies and is encountered in murine liver tumors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{noguchi_fantom5_2017,

title = {FANTOM5 CAGE profiles of human and mouse samples},

author = {Noguchi, Shuhei and Arakawa, Takahiro and Fukuda, Shiro and Furuno, Masaaki and Hasegawa, Akira and Hori, Fumi and Ishikawa-Kato, Sachi and Kaida, Kaoru and Kaiho, Ai and Kanamori-Katayama, Mutsumi and Kawashima, Tsugumi and Kojima, Miki and Kubosaki, Atsutaka and Manabe, Ri-ichiroh and Murata, Mitsuyoshi and Nagao-Sato, Sayaka and Nakazato, Kenichi and Ninomiya, Noriko and Nishiyori-Sueki, Hiromi and Noma, Shohei and Saijyo, Eri and Saka, Akiko and Sakai, Mizuho and Simon, Christophe and Suzuki, Naoko and Tagami, Michihira and Watanabe, Shoko and Yoshida, Shigehiro and Arner, Peter and Axton, Richard A. and Babina, Magda and Baillie, J. Kenneth and Barnett, Timothy C. and Beckhouse, Anthony G. and Blumenthal, Antje and Bodega, Beatrice and Bonetti, Alessandro and Briggs, James and Brombacher, Frank and Carlisle, Ailsa J. and Clevers, Hans C. and Davis, Carrie A. and Detmar, Michael and Dohi, Taeko and Edge, Albert S. B. and Edinger, Matthias and Ehrlund, Anna and Ekwall, Karl and Endoh, Mitsuhiro and Enomoto, Hideki and Eslami, Afsaneh and Fagiolini, Michela and Fairbairn, Lynsey and Farach-Carson, Mary C. and Faulkner, Geoffrey J.},

doi = {10.1038/sdata.2017.112},

issn = {2052-4463},

year  = {2017},

date = {2017-08-29},

journal = {Scientific Data},

volume = {4},

pages = {170112},

abstract = {In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Richardson2017-hr,

title = {Heritable L1 retrotransposition in the mouse primordial  germline and early embryo},

author = {Sandra R Richardson and Patricia Gerdes and Daniel J Gerhardt and Francisco J Sanchez-Luque and Gabriela-Oana Bodea and Martin Mu{~n}oz-Lopez and Samuel J Jesuadian and Marie-Jeanne H C Kempen and Patricia E Carreira and Jeffrey A Jeddeloh and Jose L Garcia-Perez and Haig H Kazazian Jr and Adam D Ewing and Geoffrey J Faulkner},

url = {http://dx.doi.org/10.1101/gr.219022.116},

year  = {2017},

date = {2017-08-01},

journal = {Genome Res.},

volume = {27},

number = {8},

pages = {1395--1405},

abstract = {LINE-1 (L1) retrotransposons are a noted source of genetic 

 diversity and disease in mammals. To expand its genomic 

 footprint, L1 must mobilize in cells that will contribute 

 their genetic material to subsequent generations. Heritable L1 

 insertions may therefore arise in germ cells and in 

 pluripotent embryonic cells, prior to germline specification, 

 yet the frequency and predominant developmental timing of such 

 events remain unclear. Here, we applied mouse retrotransposon 

 capture sequencing (mRC-seq) and whole-genome sequencing (WGS) 

 to pedigrees of C57BL/6J animals, and uncovered an L1 

 insertion rate of $geq$1 event per eight births. We traced 

 heritable L1 insertions to pluripotent embryonic cells and, 

 strikingly, to early primordial germ cells (PGCs). New L1 

 insertions bore structural hallmarks of target-site primed 

 reverse transcription (TPRT) and mobilized efficiently in a 

 cultured cell retrotransposition assay. Together, our results 

 highlight the rate and evolutionary impact of heritable L1 

 retrotransposition and reveal retrotransposition-mediated 

 genomic diversification as a fundamental property of 

 pluripotent embryonic cells in vivo.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rava2017-wf,

title = {Mutual epithelium-macrophage dependency in liver  carcinogenesis mediated by ST18},

author = {Micol Rav\`{a} and Aleco D'Andrea and Mirko Doni and Theresia R Kress and Renato Ostuni and Valerio Bianchi and Marco J Morelli and Agnese Collino and Serena Ghisletti and Paola Nicoli and Camilla Recordati and Maria Iascone and Aurelio Sonzogni and Lorenzo D'Antiga and Ruchi Shukla and Geoffrey J Faulkner and Gioacchino Natoli and Stefano Campaner and Bruno Amati},

url = {http://dx.doi.org/10.1002/hep.28942},

year  = {2017},

date = {2017-05-01},

journal = {Hepatology},

volume = {65},

number = {5},

pages = {1708--1719},

abstract = {The ST18 gene has been proposed to act either as a tumor 

 suppressor or as an oncogene in different human cancers, but 

 direct evidence for its role in tumorigenesis has been lacking 

 thus far. Here, we demonstrate that ST18 is critical for tumor 

 progression and maintenance in a mouse model of liver cancer, 

 based on oncogenic transformation and adoptive transfer of 

 primary precursor cells (hepatoblasts). ST18 messenger RNA 

 (mRNA) and protein were detectable neither in normal liver nor 

 in cultured hepatoblasts, but were readily expressed after 

 subcutaneous engraftment and tumor growth. ST18 expression in 

 liver cells was induced by inflammatory cues, including acute 

 or chronic inflammation in vivo, as well as coculture with 

 macrophages in vitro. Knocking down the ST18 mRNA in 

 transplanted hepatoblasts delayed tumor progression. Induction 

 of ST18 knockdown in pre-established tumors caused rapid tumor 

 involution associated with pervasive morphological changes, 

 proliferative arrest, and apoptosis in tumor cells, as well as 

 depletion of tumor-associated macrophages, vascular ectasia, 

 and hemorrhage. Reciprocally, systemic depletion of 

 macrophages in recipient animals had very similar phenotypic 

 consequences, impairing either tumor development or 

 maintenance, and suppressing ST18 expression in hepatoblasts. 

 Finally, RNA sequencing of ST18-depleted tumors before 

 involution revealed down-regulation of inflammatory response 

 genes, pointing to the suppression of nuclear factor kappa 

 B-dependent transcription. CONCLUSION: ST18 expression in 

 epithelial cells is induced by tumor-associated macrophages, 

 contributing to the reciprocal feed-forward loop between both 

 cell types in liver tumorigenesis. Our findings warrant the 

 exploration of means to interfere with ST18-dependent 

 epithelium-macrophage interactions in a therapeutic setting. 

 (Hepatology 2017;65:1708-1719).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Baillie2017-es,

title = {Analysis of the human monocyte-derived macrophage 

 transcriptome and response to lipopolysaccharide provides new 

 insights into genetic aetiology of inflammatory bowel disease},

author = {Kenneth J Baillie and Erik Arner and Carsten Daub and Michiel De Hoon and Masayoshi Itoh and Hideya Kawaji and Timo Lassmann and Piero Carninci and Alistair R R Forrest and Yoshihide Hayashizaki and FANTOM Consortium and Geoffrey J Faulkner and Christine A Wells and Michael Rehli and Paul Pavli and Kim M Summers and David A Hume},

url = {http://dx.doi.org/10.1371/journal.pgen.1006641},

year  = {2017},

date = {2017-03-01},

journal = {PLoS Genet.},

volume = {13},

number = {3},

pages = {e1006641},

abstract = {The FANTOM5 consortium utilised cap analysis of gene 

 expression (CAGE) to provide an unprecedented insight into 

 transcriptional regulation in human cells and tissues. In the 

 current study, we have used CAGE-based transcriptional 

 profiling on an extended dense time course of the response of 

 human monocyte-derived macrophages grown in macrophage 

 colony-stimulating factor (CSF1) to bacterial 

 lipopolysaccharide (LPS). We propose that this system provides 

 a model for the differentiation and adaptation of monocytes 

 entering the intestinal lamina propria. The response to LPS is 

 shown to be a cascade of successive waves of transient gene 

 expression extending over at least 48 hours, with hundreds of 

 positive and negative regulatory loops. Promoter analysis 

 using motif activity response analysis (MARA) identified some 

 of the transcription factors likely to be responsible for the 

 temporal profile of transcriptional activation. Each 

 LPS-inducible locus was associated with multiple inducible 

 enhancers, and in each case, transient eRNA transcription at 

 multiple sites detected by CAGE preceded the appearance of 

 promoter-associated transcripts. LPS-inducible long non-coding 

 RNAs were commonly associated with clusters of inducible 

 enhancers. We used these data to re-examine the hundreds of 

 loci associated with susceptibility to inflammatory bowel 

 disease (IBD) in genome-wide association studies. Loci 

 associated with IBD were strongly and specifically (relative 

 to rheumatoid arthritis and unrelated traits) enriched for 

 promoters that were regulated in monocyte differentiation or 

 activation. Amongst previously-identified IBD susceptibility 

 loci, the vast majority contained at least one promoter that 

 was regulated in CSF1-dependent monocyte-macrophage 

 transitions and/or in response to LPS. On this basis, we 

 concluded that IBD loci are strongly-enriched for 

 monocyte-specific genes, and identified at least 134 

 additional candidate genes associated with IBD susceptibility 

 from reanalysis of published GWA studies. We propose that 

 dysregulation of monocyte adaptation to the environment of the 

 gastrointestinal mucosa is the key process leading to 

 inflammatory bowel disease.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Wolf2017-iq,

title = {On the role of H3.3 in retroviral silencing},

author = {Gernot Wolf and Rita Rebollo and Mohammad M Karimi and Adam D Ewing and Rui Kamada and Warren Wu and Brenda Wu and Mahesh Bachu and Keiko Ozato and Geoffrey J Faulkner and Dixie L Mager and Matthew C Lorincz and Todd S Macfarlan},

url = {http://dx.doi.org/10.1038/nature23277},

year  = {2017},

date = {2017-01-01},

journal = {Nature},

volume = {548},

number = {7665},

pages = {E1--E3},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Faulkner2017-cs,

title = {L1 Mosaicism in Mammals: Extent, Effects, and Evolution},

author = {Geoffrey J Faulkner and Jose L Garcia-Perez},

url = {http://dx.doi.org/10.1016/j.tig.2017.07.004},

year  = {2017},

date = {2017-01-01},

journal = {Trends Genet.},

volume = {33},

number = {11},

pages = {802--816},

abstract = {The retrotransposon LINE-1 (long interspersed element 1, L1) 

 is a transposable element that has extensively colonized the 

 mammalian germline. L1 retrotransposition can also occur in 

 somatic cells, causing genomic mosaicism, as well as in 

 cancer. However, the extent of L1-driven mosaicism arising 

 during ontogenesis is unclear. We discuss here recent 

 experimental data which, at a minimum, fully substantiate L1 

 mosaicism in early embryonic development and neural cells, 

 including post-mitotic neurons. We also consider the possible 

 biological impact of somatic L1 insertions in neurons, the 

 existence of donor L1s that are highly active ('hot') in 

 specific spatiotemporal niches, and the evolutionary selection 

 of donor L1s driving neuronal mosaicism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Li2016-ug,

title = {Point Mutations in Exon 1B of APC Reveal Gastric 

 Adenocarcinoma and Proximal Polyposis of the Stomach as a 

 Familial Adenomatous Polyposis Variant},

author = {Jun Li and Susan L Woods and Sue Healey and Jonathan Beesley and Xiaoqing Chen and Jason S Lee and Haran Sivakumaran and Nicci Wayte and Katia Nones and Joshua J Waterfall and John Pearson and Anne-Marie Patch and Janine Senz and Manuel A Ferreira and Pardeep Kaurah and Robertson Mackenzie and Alireza Heravi-Moussavi and Samantha Hansford and Tamsin R M Lannagan and Amanda B Spurdle and Peter T Simpson and Leonard da Silva and Sunil R Lakhani and Andrew D Clouston and Mark Bettington and Florian Grimpen and Rita A Busuttil and Natasha Di Costanzo and Alex Boussioutas and Marie Jeanjean and George Chong and Aur\'{e}lie Fabre and Sylviane Olschwang and Geoffrey J Faulkner and Evangelos Bellos and Lachlan Coin and Kevin Rioux and Oliver F Bathe and Xiaogang Wen and Hilary C Martin and Deborah W Neklason and Sean R Davis and Robert L Walker and Kathleen A Calzone and Itzhak Avital and Theo Heller and Christopher Koh and Marbin Pineda and Udo Rudloff and Martha Quezado and Pavel N Pichurin and Peter J Hulick and Scott M Weissman and Anna Newlin and Wendy S Rubinstein and Jone E Sampson and Kelly Hamman and David Goldgar and Nicola Poplawski and Kerry Phillips and Lyn Schofield and Jacqueline Armstrong and Cathy Kiraly-Borri and Graeme K Suthers and David G Huntsman and William D Foulkes and Fatima Carneiro and Noralane M Lindor and Stacey L Edwards and Juliet D French and Nicola Waddell and Paul S Meltzer and Daniel L Worthley and Kasmintan A Schrader and Georgia Chenevix-Trench},

url = {http://dx.doi.org/10.1016/j.ajhg.2016.03.001},

year  = {2016},

date = {2016-05-01},

journal = {Am. J. Hum. Genet.},

volume = {98},

number = {5},

pages = {830--842},

abstract = {Gastric adenocarcinoma and proximal polyposis of the stomach 

 (GAPPS) is an autosomal-dominant cancer-predisposition 

 syndrome with a significant risk of gastric, but not 

 colorectal, adenocarcinoma. We mapped the gene to 5q22 and 

 found loss of the wild-type allele on 5q in fundic gland 

 polyps from affected individuals. Whole-exome and -genome 

 sequencing failed to find causal mutations but, through Sanger 

 sequencing, we identified point mutations in APC promoter 1B 

 that co-segregated with disease in all six families. The 

 mutations reduced binding of the YY1 transcription factor and 

 impaired activity of the APC promoter 1B in luciferase assays. 

 Analysis of blood and saliva from carriers showed allelic 

 imbalance of APC, suggesting that these mutations lead to 

 decreased allele-specific expression in vivo. Similar 

 mutations in APC promoter 1B occur in rare families with 

 familial adenomatous polyposis (FAP). Promoter 1A is 

 methylated in GAPPS and sporadic FGPs and in normal stomach, 

 which suggests that 1B transcripts are more important than 1A 

 in gastric mucosa. This might explain why all known 

 GAPPS-affected families carry promoter 1B point mutations but 

 only rare FAP-affected families carry similar mutations, the 

 colonic cells usually being protected by the expression of the 

 1A isoform. Gastric polyposis and cancer have been previously 

 described in some FAP-affected individuals with large 

 deletions around promoter 1B. Our finding that GAPPS is caused 

 by point mutations in the same promoter suggests that families 

 with mutations affecting the promoter 1B are at risk of 

 gastric adenocarcinoma, regardless of whether or not 

 colorectal polyps are present.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Gerdes2016-yk,

title = {Transposable elements in the mammalian embryo: pioneers 

 surviving through stealth and service},

author = {Patricia Gerdes and Sandra R Richardson and Dixie L Mager and Geoffrey J Faulkner},

url = {http://dx.doi.org/10.1186/s13059-016-0965-5},

year  = {2016},

date = {2016-05-01},

journal = {Genome Biol.},

volume = {17},

pages = {100},

abstract = {Transposable elements (TEs) are notable drivers of genetic 

 innovation. Over evolutionary time, TE insertions can supply 

 new promoter, enhancer, and insulator elements to 

 protein-coding genes and establish novel, species-specific 

 gene regulatory networks. Conversely, ongoing TE-driven 

 insertional mutagenesis, nonhomologous recombination, and 

 other potentially deleterious processes can cause sporadic 

 disease by disrupting genome integrity or inducing abrupt gene 

 expression changes. Here, we discuss recent evidence 

 suggesting that TEs may contribute regulatory innovation to 

 mammalian embryonic and pluripotent states as a means to ward 

 off complete repression by their host genome.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Gerdes2016-ga,

title = {TET enzymes: double agents in the transposable element-host 

 genome conflict},

author = {Patricia Gerdes and Sandra R Richardson and Geoffrey J Faulkner},

url = {http://dx.doi.org/10.1186/s13059-016-1124-8},

year  = {2016},

date = {2016-01-01},

journal = {Genome Biol.},

volume = {17},

number = {1},

pages = {259},

abstract = {The mouse genome is replete with retrotransposon sequences, 

 from evolutionarily young elements with mutagenic potential 

 that must be controlled, to inactive molecular fossils whose 

 sequences can be domesticated over evolutionary time to 

 benefit the host genome. In an exciting new study, de la Rica 

 and colleagues have uncovered a complex relationship between 

 ten-eleven translocation (TET) proteins and retrotransposons 

 in mouse embryonic stem cells (ESCs), implicating TETs as 

 enhancers in the exaptation and function of retroelement 

 sequences. Furthermore, they have demonstrated that active 

 demethylation of retrotransposons does not correlate with 

 their increased expression in ESCs, calling into question 

 long-held assumptions regarding the importance of DNA 

 demethylation for retrotransposon expression, and revealing 

 novel epigenetic players in retrotransposon control.Please see 

 related Research article: 

 http://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1096-8.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Sanchez-Luque2016-vi,

title = {Retrotransposon Capture Sequencing (RC-Seq): A Targeted, 

 High-Throughput Approach to Resolve Somatic L1 

 Retrotransposition in Humans},

author = {Francisco J Sanchez-Luque and Sandra R Richardson and Geoffrey J Faulkner},

url = {http://dx.doi.org/10.1007/978-1-4939-3372-3_4},

year  = {2016},

date = {2016-01-01},

journal = {Methods Mol. Biol.},

volume = {1400},

pages = {47--77},

abstract = {Mobile genetic elements (MGEs) are of critical importance in 

 genomics and developmental biology. Polymorphic and somatic 

 MGE insertions have the potential to impact the phenotype of 

 an individual, depending on their genomic locations and 

 functional consequences. However, the identification of 

 polymorphic and somatic insertions among the plethora of 

 copies residing in the genome presents a formidable technical 

 challenge. Whole genome sequencing has the potential to 

 address this problem; however, its efficacy depends on the 

 abundance of cells carrying the new insertion. Robust 

 detection of somatic insertions present in only a subset of 

 cells within a given sample can also be prohibitively 

 expensive due to a requirement for high sequencing depth. 

 Here, we describe retrotransposon capture sequencing (RC-seq), 

 a sequence capture approach in which Illumina libraries are 

 enriched for fragments containing the 5' and 3' termini of 

 specific MGEs. RC-seq allows the detection of known 

 polymorphic insertions present in an individual, as well as 

 the identification of rare or private germline insertions not 

 previously described. Furthermore, RC-seq can be used to 

 detect and characterize somatic insertions, providing a 

 valuable tool to elucidate the extent and characteristics of 

 MGE activity in healthy tissues and in various disease states.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Klawitter2016-ur,

title = {Reprogramming triggers endogenous L1 and Alu  retrotransposition in human induced pluripotent stem cells},

author = {Sabine Klawitter and Nina V Fuchs and Kyle R Upton and Martin Mu{~n}oz-Lopez and Ruchi Shukla and Jichang Wang and Marta Garcia-Ca{~n}adas and Cesar Lopez-Ruiz and Daniel J Gerhardt and Attila Sebe and Ivana Grabundzija and Sylvia Merkert and Patricia Gerdes and Andres J Pulgarin and Anja Bock and Ulrike Held and Anett Witthuhn and Alexandra Haase and Bal\'{a}zs Sarkadi and Johannes L\"{o}wer and Ernst J Wolvetang and Ulrich Martin and Zolt\'{a}n Ivics and Zsuzsanna Izsv\'{a}k and Jose L Garcia-Perez and Geoffrey J Faulkner and Gerald G Schumann},

url = {http://dx.doi.org/10.1038/ncomms10286},

year  = {2016},

date = {2016-01-01},

journal = {Nat. Commun.},

volume = {7},

pages = {10286},

abstract = {Human induced pluripotent stem cells (hiPSCs) are capable of 

 unlimited proliferation and can differentiate in vitro to 

 generate derivatives of the three primary germ layers. Genetic 

 and epigenetic abnormalities have been reported by Wissing and 

 colleagues to occur during hiPSC derivation, including 

 mobilization of engineered LINE-1 (L1) retrotransposons. 

 However, incidence and functional impact of endogenous 

 retrotransposition in hiPSCs are yet to be established. Here 

 we apply retrotransposon capture sequencing to eight hiPSC 

 lines and three human embryonic stem cell (hESC) lines, 

 revealing endogenous L1, Alu and SINE-VNTR-Alu (SVA) 

 mobilization during reprogramming and pluripotent stem cell 

 cultivation. Surprisingly, 4/7 de novo L1 insertions are full 

 length and 6/11 retrotransposition events occurred in 

 protein-coding genes expressed in pluripotent stem cells. We 

 further demonstrate that an intronic L1 insertion in the 

 CADPS2 gene is acquired during hiPSC cultivation and disrupts 

 CADPS2 expression. These experiments elucidate endogenous 

 retrotransposition, and its potential consequences, in hiPSCs 

 and hESCs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{sanchez-luque_retrotransposon_2016,

title = {Retrotransposon Capture Sequencing (RC-Seq): A Targeted, High-Throughput Approach to Resolve Somatic L1 Retrotransposition in Humans},

author = {Francisco J Sanchez-Luque and Sandra R Richardson and Geoffrey J Faulkner},

doi = {10.1007/978-1-4939-3372-3_4},

issn = {1940-6029},

year  = {2016},

date = {2016-01-01},

journal = {Methods in Molecular Biology (Clifton, N.J.)},

volume = {1400},

pages = {47--77},

abstract = {Mobile genetic elements (MGEs) are of critical importance in genomics and developmental biology. Polymorphic and somatic MGE insertions have the potential to impact the phenotype of an individual, depending on their genomic locations and functional consequences. However, the identification of polymorphic and somatic insertions among the plethora of copies residing in the genome presents a formidable technical challenge. Whole genome sequencing has the potential to address this problem; however, its efficacy depends on the abundance of cells carrying the new insertion. Robust detection of somatic insertions present in only a subset of cells within a given sample can also be prohibitively expensive due to a requirement for high sequencing depth. Here, we describe retrotransposon capture sequencing (RC-seq), a sequence capture approach in which Illumina libraries are enriched for fragments containing the 5' and 3' termini of specific MGEs. RC-seq allows the detection of known polymorphic insertions present in an individual, as well as the identification of rare or private germline insertions not previously described. Furthermore, RC-seq can be used to detect and characterize somatic insertions, providing a valuable tool to elucidate the extent and characteristics of MGE activity in healthy tissues and in various disease states.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Carreira2016-vr,

title = {Evidence for L1-associated DNA rearrangements and negligible  L1 retrotransposition in glioblastoma multiforme},

author = {Patricia E Carreira and Adam D Ewing and Guibo Li and Stephanie N Schauer and Kyle R Upton and Allister C Fagg and Santiago Morell and Michaela Kindlova and Patricia Gerdes and Sandra R Richardson and Bo Li and Daniel J Gerhardt and Jun Wang and Paul M Brennan and Geoffrey J Faulkner},

url = {http://dx.doi.org/10.1186/s13100-016-0076-6},

year  = {2016},

date = {2016-01-01},

journal = {Mob. DNA},

volume = {7},

number = {1},

pages = {21},

abstract = {LINE-1 (L1) retrotransposons are a notable endogenous source of 

 mutagenesis in mammals. Notably, cancer cells can support unusual 

 L1 retrotransposition and L1-associated sequence rearrangement 

 mechanisms following DNA damage. Recent reports suggest that L1 

 is mobile in epithelial tumours and neural cells but, 

 paradoxically, not in brain cancers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Upton2015-qu,

title = {Ubiquitous L1 mosaicism in hippocampal neurons},

author = {Kyle R Upton and Daniel J Gerhardt and Samuel J Jesuadian and Sandra R Richardson and Francisco J S\'{a}nchez-Luque and Gabriela O Bodea and Adam D Ewing and Carmen Salvador-Palomeque and Marjo S van der Knaap and Paul M Brennan and Adeline Vanderver and Geoffrey J Faulkner},

url = {http://dx.doi.org/10.1016/j.cell.2015.03.026},

year  = {2015},

date = {2015-04-01},

journal = {Cell},

volume = {161},

number = {2},

pages = {228--239},

abstract = {Somatic LINE-1 (L1) retrotransposition during neurogenesis is 

 a potential source of genotypic variation among neurons. As a 

 neurogenic niche, the hippocampus supports pronounced L1 

 activity. However, the basal parameters and biological impact 

 of L1-driven mosaicism remain unclear. Here, we performed 

 single-cell retrotransposon capture sequencing (RC-seq) on 

 individual human hippocampal neurons and glia, as well as 

 cortical neurons. An estimated 13.7 somatic L1 insertions 

 occurred per hippocampal neuron and carried the sequence 

 hallmarks of target-primed reverse transcription. Notably, 

 hippocampal neuron L1 insertions were specifically enriched in 

 transcribed neuronal stem cell enhancers and hippocampus 

 genes, increasing their probability of functional relevance. 

 In addition, bias against intronic L1 insertions sense 

 oriented relative to their host gene was observed, perhaps 

 indicating moderate selection against this configuration in 

 vivo. These experiments demonstrate pervasive L1 mosaicism at 

 genomic loci expressed in hippocampal neurons.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Arner2015-de,

title = {Transcribed enhancers lead waves of coordinated transcription in 

 transitioning mammalian cells},

author = {Erik Arner and Carsten O Daub and Kristoffer Vitting-Seerup and Robin Andersson and Berit Lilje and Finn Drabl{\o}s and Andreas Lennartsson and Michelle R\"{o}nnerblad and Olga Hrydziuszko and Morana Vitezic and Tom C Freeman and Ahmad M N Alhendi and Peter Arner and Richard Axton and Kenneth J Baillie and Anthony Beckhouse and Beatrice Bodega and James Briggs and Frank Brombacher and Margaret Davis and Michael Detmar and Anna Ehrlund and Mitsuhiro Endoh and Afsaneh Eslami and Michela Fagiolini and Lynsey Fairbairn and Geoffrey J Faulkner and Carmelo Ferrai and Malcolm E Fisher and Lesley Forrester and Daniel Goldowitz and Reto Guler and Thomas Ha and Mitsuko Hara and Meenhard Herlyn and Tomokatsu Ikawa and Chieko Kai and Hiroshi Kawamoto and Levon M Khachigian and Peter S Klinken and Soichi Kojima and Haruhiko Koseki and Sarah Klein and Niklas Mejhert and Ken Miyaguchi and Yosuke Mizuno and Mitsuru Morimoto and Kelly J Morris and Christine Mummery and Yutaka Nakachi and Soichi Ogishima and Mariko Okada-Hatakeyama and Yasushi Okazaki and Valerio Orlando and Dmitry Ovchinnikov and Robert Passier and Margaret Patrikakis and Ana Pombo and Xian-Yang Qin and Sugata Roy and Hiroki Sato and Suzana Savvi and Alka Saxena and Anita Schwegmann and Daisuke Sugiyama and Rolf Swoboda and Hiroshi Tanaka and Andru Tomoiu and Louise N Winteringham and Ernst Wolvetang and Chiyo Yanagi-Mizuochi and Misako Yoneda and Susan Zabierowski and Peter Zhang and Imad Abugessaisa and Nicolas Bertin and Alexander D Diehl and Shiro Fukuda and Masaaki Furuno and Jayson Harshbarger and Akira Hasegawa and Fumi Hori and Sachi Ishikawa-Kato and Yuri Ishizu and Masayoshi Itoh and Tsugumi Kawashima and Miki Kojima and Naoto Kondo and Marina Lizio and Terrence F Meehan and Christopher J Mungall and Mitsuyoshi Murata and Hiromi Nishiyori-Sueki and Serkan Sahin and Sayaka Nagao-Sato and Jessica Severin and Michiel J L de Hoon and Jun Kawai and Takeya Kasukawa and Timo Lassmann and Harukazu Suzuki and Hideya Kawaji and Kim M Summers and Christine Wells and FANTOM Consortium and David A Hume and Alistair R R Forrest and Albin Sandelin and Piero Carninci and Yoshihide Hayashizaki},

url = {http://dx.doi.org/10.1126/science.1259418},

year  = {2015},

date = {2015-01-01},

journal = {Science},

volume = {347},

number = {6225},

pages = {1010--1014},

abstract = {Although it is generally accepted that cellular differentiation 

 requires changes to transcriptional networks, dynamic regulation 

 of promoters and enhancers at specific sets of genes has not been 

 previously studied en masse. Exploiting the fact that active 

 promoters and enhancers are transcribed, we simultaneously 

 measured their activity in 19 human and 14 mouse time courses 

 covering a wide range of cell types and biological stimuli. 

 Enhancer RNAs, then messenger RNAs encoding transcription 

 factors, dominated the earliest responses. Binding sites for key 

 lineage transcription factors were simultaneously overrepresented 

 in enhancers and promoters active in each cellular system. Our 

 data support a highly generalizable model in which enhancer 

 transcription is the earliest event in successive waves of 

 transcriptional change during cellular differentiation or 

 activation.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Upton2014-zu,

title = {Blood from 'junk': the LTR chimeric transcript Pu.2 promotes 

 erythropoiesis},

author = {Kyle R Upton and Geoffrey J Faulkner},

url = {http://dx.doi.org/10.1186/1759-8753-5-15},

year  = {2014},

date = {2014-05-01},

journal = {Mob. DNA},

volume = {5},

pages = {15},

abstract = {Transposable elements (TEs) are a prominent feature of most 

 eukaryotic genomes. Despite rapidly accumulating evidence for 

 the role of TE-driven insertional mutagenesis and structural 

 variation in genome evolution, few clear examples of 

 individual TEs impacting biology via perturbed gene regulation 

 are available. A recent report describes the discovery of an 

 alternative promoter for the murine erythroid transcription 

 factor Pu.1. This promoter is located in an ORR1A0 long 

 terminal repeat (LTR) retrotransposon intronic to Pu.1 and is 

 regulated by the Kr\"{u}ppel-like factors KLF1 and KLF3. 

 Expression of the resultant chimeric transcript, called Pu.2, 

 spontaneously induces erythroid differentiation in vitro. 

 These experiments illustrate how transcription factor binding 

 sites spread by retrotransposition have the potential to 

 impact networks encoding key biological processes in the host 

 genome.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Richardson2014-yj,

title = {Diversity through duplication: whole-genome sequencing reveals 

 novel gene retrocopies in the human population},

author = {Sandra R Richardson and Carmen Salvador-Palomeque and Geoffrey J Faulkner},

url = {http://dx.doi.org/10.1002/bies.201300181},

year  = {2014},

date = {2014-05-01},

journal = {Bioessays},

volume = {36},

number = {5},

pages = {475--481},

abstract = {Gene retrocopies are generated by reverse transcription and 

 genomic integration of mRNA. As such, retrocopies present an 

 important exception to the central dogma of molecular biology, 

 and have substantially impacted the functional landscape of 

 the metazoan genome. While an estimated 8,000-17,000 

 retrocopies exist in the human genome reference sequence, the 

 extent of variation between individuals in terms of retrocopy 

 content has remained largely unexplored. Three recent studies 

 by Abyzov et al., Ewing et al. and Schrider et al. have 

 exploited 1,000 Genomes Project Consortium data, as well as 

 other sources of whole-genome sequencing data, to uncover 

 novel gene retrocopies. Here, we compare the methods and 

 results of these three studies, highlight the impact of 

 retrocopies in human diversity and genome evolution, and 

 speculate on the potential for somatic gene retrocopies to 

 impact cancer etiology and genetic diversity among individual 

 neurons in the mammalian brain.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Consortium2014,

title = {A promoter-level mammalian expression atlas},

author = {{FANTOM Consortium and RIKEN the PMI and CLST (DGT)} and Alistair R R Forrest and Hideya Kawaji and ... and Geoffrey J Faulkner and ... and David A Hume and Piero Carninci and Yoshihide Hayashizaki},

url = {http://www.ncbi.nlm.nih.gov/pubmed/24670764},

doi = {10.1038/nature13182},

year  = {2014},

date = {2014-03-26},

journal = {Nature},

volume = {507},

number = {7493},

pages = {462-470},

abstract = {Regulated transcription controls the diversity, developmental

              pathways and spatial organization of the hundreds of cell types

              that make up a mammal. Using single-molecule cDNA sequencing, we

              mapped transcription start sites (TSSs) and their usage in human

              and mouse primary cells, cell lines and tissues to produce a

              comprehensive overview of mammalian gene expression across the

              human body. We find that few genes are truly 'housekeeping',

              whereas many mammalian promoters are composite entities composed

              of several closely separated TSSs, with independent

              cell-type-specific expression profiles. TSSs specific to

              different cell types evolve at different rates, whereas promoters

              of broadly expressed genes are the most conserved. Promoter-based

              expression analysis reveals key transcription factors defining

              cell states and links them to binding-site motifs. The functions

              of identified novel transcripts can be predicted by coexpression

              and sample ontology enrichment analyses. The functional

              annotation of the mammalian genome 5 (FANTOM5) project provides

              comprehensive expression profiles and functional annotation of

              mammalian cell-type-specific transcriptomes with wide

              applications in biomedical research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pascarella2014-oq,

title = {NanoCAGE analysis of the mouse olfactory epithelium 

 identifies the expression of vomeronasal receptors and of 

 proximal LINE elements},

author = {Giovanni Pascarella and Dejan Lazarevic and Charles Plessy and Nicolas Bertin and Altuna Akalin and Christina Vlachouli and Roberto Simone and Geoffrey J Faulkner and Silvia Zucchelli and Jun Kawai and Carsten O Daub and Yoshihide Hayashizaki and Boris Lenhard and Piero Carninci and Stefano Gustincich},

url = {http://dx.doi.org/10.3389/fncel.2014.00041},

year  = {2014},

date = {2014-02-01},

journal = {Front. Cell. Neurosci.},

volume = {8},

pages = {41},

abstract = {By coupling laser capture microdissection to nanoCAGE 

 technology and next-generation sequencing we have identified 

 the genome-wide collection of active promoters in the mouse 

 Main Olfactory Epithelium (MOE). Transcription start sites 

 (TSSs) for the large majority of Olfactory Receptors (ORs) 

 have been previously mapped increasing our understanding of 

 their promoter architecture. Here we show that in our nanoCAGE 

 libraries of the mouse MOE we detect a large number of tags 

 mapped in loci hosting Type-1 and Type-2 Vomeronasal Receptors 

 genes (V1Rs and V2Rs). These loci also show a massive 

 expression of Long Interspersed Nuclear Elements (LINEs). We 

 have validated the expression of selected receptors detected 

 by nanoCAGE with in situ hybridization, RT-PCR and qRT-PCR. 

 This work extends the repertory of receptors capable of 

 sensing chemical signals in the MOE, suggesting intriguing 

 interplays between MOE and VNO for pheromone processing and 

 positioning transcribed LINEs as candidate regulatory RNAs for 

 VRs expression.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Richardson2014-nf,

title = {L1 retrotransposons and somatic mosaicism in the brain},

author = {Sandra R Richardson and Santiago Morell and Geoffrey J Faulkner},

url = {http://dx.doi.org/10.1146/annurev-genet-120213-092412},

year  = {2014},

date = {2014-01-01},

journal = {Annu. Rev. Genet.},

volume = {48},

pages = {1--27},

abstract = {Long interspersed element 1 (LINE-1 or L1) retrotransposons 

 have generated one-third of the human genome, and their 

 ongoing mobility is a source of inter- and intraindividual 

 genetic diversity. Although retrotransposition in metazoans 

 has long been considered a germline phenomenon, recent 

 experiments using cultured cells, animal models, and human 

 tissues have revealed extensive L1 mobilization in rodent and 

 human neurons, as well as mobile element activity in the 

 Drosophila brain. In this review, we evaluate the available 

 evidence for L1 retrotransposition in the brain and discuss 

 mechanisms that may regulate neuronal retrotransposition in 

 vivo. We compare experimental strategies used to map de novo 

 somatic retrotransposition events and present the optimal 

 criteria to identify a somatic L1 insertion. Finally, we 

 discuss the unresolved impact of L1-mediated somatic mosaicism 

 upon normal neurobiology, as well as its potential to drive 

 neurological disease.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Carreira2014-oa,

title = {L1 retrotransposons, cancer stem cells and oncogenesis},

author = {Patricia E Carreira and Sandra R Richardson and Geoffrey J Faulkner},

url = {http://dx.doi.org/10.1111/febs.12601},

year  = {2014},

date = {2014-01-01},

journal = {FEBS J.},

volume = {281},

number = {1},

pages = {63--73},

abstract = {Retrotransposons have played a central role in human genome 

 evolution. The accumulation of heritable L1, Alu and SVA 

 retrotransposon insertions continues to generate structural 

 variation within and between populations, and can result in 

 spontaneous genetic disease. Recent works have reported 

 somatic L1 retrotransposition in tumours, which in some cases 

 may contribute to oncogenesis. Intriguingly, L1 mobilization 

 appears to occur almost exclusively in cancers of epithelial 

 cell origin. In this review, we discuss how L1 

 retrotransposition could potentially trigger neoplastic 

 transformation, based on the established correlation between 

 L1 activity and cellular plasticity, and the proven capacity 

 of L1-mediated insertional mutagenesis to decisively alter 

 gene expression and functional output.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Faulkner2013-sf,

title = {Retrotransposon silencing during embryogenesis: dicer cuts in 

 LINE},

author = {Geoffrey J Faulkner},

url = {http://dx.doi.org/10.1371/journal.pgen.1003944},

year  = {2013},

date = {2013-11-01},

journal = {PLoS Genet.},

volume = {9},

number = {11},

pages = {e1003944},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Reilly2013-ne,

title = {The role of transposable elements in health and diseases of 

 the central nervous system},

author = {Matthew T Reilly and Geoffrey J Faulkner and Joshua Dubnau and Igor Ponomarev and Fred H Gage},

url = {http://dx.doi.org/10.1523/JNEUROSCI.3369-13.2013},

year  = {2013},

date = {2013-11-01},

journal = {J. Neurosci.},

volume = {33},

number = {45},

pages = {17577--17586},

abstract = {First discovered in maize by Barbara McClintock in the 1940s, 

 transposable elements (TEs) are DNA sequences that in some 

 cases have the ability to move along chromosomes or 

 ``transpose'' in the genome. This revolutionary finding was 

 initially met with resistance by the scientific community and 

 viewed by some as heretical. A large body of knowledge has 

 accumulated over the last 60 years on the biology of TEs. 

 Indeed, it is now known that TEs can generate genomic 

 instability and reconfigure gene expression networks both in 

 the germline and somatic cells. This review highlights recent 

 findings on the role of TEs in health and diseases of the CNS, 

 which were presented at the 2013 Society for Neuroscience 

 meeting. The work of the speakers in this symposium shows that 

 TEs are expressed and active in the brain, challenging the 

 dogma that neuronal genomes are static and revealing that they 

 are susceptible to somatic genomic alterations. These new 

 findings on TE expression and function in the CNS have major 

 implications for understanding the neuroplasticity of the 

 brain, which could hypothetically have a role in shaping 

 individual behavior and contribute to vulnerability to 

 disease.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Li2013-qx,

title = {Genome-wide methylated CpG island profiles of melanoma cells 

 reveal a melanoma coregulation network},

author = {Jian-Liang Li and Joseph Mazar and Cuncong Zhong and Geoffrey J Faulkner and Subramaniam S Govindarajan and Zhan Zhang and Marcel E Dinger and Gavin Meredith and Christopher Adams and Shaojie Zhang and John S Mattick and Animesh Ray and Ranjan J Perera},

url = {http://dx.doi.org/10.1038/srep02962},

year  = {2013},

date = {2013-01-01},

journal = {Sci. Rep.},

volume = {3},

pages = {2962},

abstract = {Metastatic melanoma is a malignant cancer with generally poor 

 prognosis, with no targeted chemotherapy. To identify 

 epigenetic changes related to melanoma, we have determined 

 genome-wide methylated CpG island distributions by 

 next-generation sequencing. Melanoma chromosomes tend to be 

 differentially methylated over short CpG island tracts. CpG 

 islands in the upstream regulatory regions of many coding and 

 noncoding RNA genes, including, for example, TERC, which 

 encodes the telomerase RNA, exhibit extensive 

 hypermethylation, whereas several repeated elements, such as 

 LINE 2, and several LTR elements, are hypomethylated in 

 advanced stage melanoma cell lines. By using CpG island 

 demethylation profiles, and by integrating these data with 

 RNA-seq data obtained from melanoma cells, we have identified 

 a co-expression network of differentially methylated genes 

 with significance for cancer related functions. Focused assays 

 of melanoma patient tissue samples for CpG island methylation 

 near the noncoding RNA gene SNORD-10 demonstrated high 

 specificity.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Shukla2013-dp,

title = {Endogenous retrotransposition activates oncogenic pathways in  hepatocellular carcinoma},

author = {Ruchi Shukla and Kyle R Upton and Martin Mu{~n}oz-Lopez and Daniel J Gerhardt and Malcolm E Fisher and Thu Nguyen and Paul M Brennan and Kenneth J Baillie and Agnese Collino and Serena Ghisletti and Shruti Sinha and Fabio Iannelli and Enrico Radaelli and Alexandre Dos Santos and Delphine Rapoud and Catherine Guettier and Didier Samuel and Gioacchino Natoli and Piero Carninci and Francesca D Ciccarelli and Jose Luis Garcia-Perez and Jamila Faivre and Geoffrey J Faulkner},

url = {http://dx.doi.org/10.1016/j.cell.2013.02.032},

year  = {2013},

date = {2013-01-01},

journal = {Cell},

volume = {153},

number = {1},

pages = {101--111},

abstract = {LINE-1 (L1) retrotransposons are mobile genetic elements 

 comprising ~17% of the human genome. New L1 insertions can 

 profoundly alter gene function and cause disease, though their 

 significance in cancer remains unclear. Here, we applied 

 enhanced retrotransposon capture sequencing (RC-seq) to 19 

 hepatocellular carcinoma (HCC) genomes and elucidated two 

 archetypal L1-mediated mechanisms enabling tumorigenesis. In 

 the first example, 4/19 (21.1%) donors presented germline 

 retrotransposition events in the tumor suppressor mutated in 

 colorectal cancers (MCC). MCC expression was ablated in each 

 case, enabling oncogenic $beta$-catenin/Wnt signaling. In the 

 second example, suppression of tumorigenicity 18 (ST18) was 

 activated by a tumor-specific L1 insertion. Experimental 

 assays confirmed that the L1 interrupted a negative feedback 

 loop by blocking ST18 repression of its enhancer. ST18 was 

 also frequently amplified in HCC nodules from Mdr2(-/-) mice, 

 supporting its assignment as a candidate liver oncogene. These 

 proof-of-principle results substantiate L1-mediated 

 retrotransposition as an important etiological factor in HCC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Solyom2012-pc,

title = {Extensive somatic L1 retrotransposition in colorectal tumors},

author = {Szilvia Solyom and Adam D Ewing and Eric P Rahrmann and Tara Doucet and Heather H Nelson and Michael B Burns and Reuben S Harris and David F Sigmon and Alex Casella and Bracha Erlanger and Sarah Wheelan and Kyle R Upton and Ruchi Shukla and Geoffrey J Faulkner and David A Largaespada and Haig H Kazazian Jr},

url = {http://dx.doi.org/10.1101/gr.145235.112},

year  = {2012},

date = {2012-12-01},

journal = {Genome Res.},

volume = {22},

number = {12},

pages = {2328--2338},

abstract = {L1 retrotransposons comprise 17% of the human genome and are 

 its only autonomous mobile elements. Although L1-induced 

 insertional mutagenesis causes Mendelian disease, their 

 mutagenic load in cancer has been elusive. Using L1-targeted 

 resequencing of 16 colorectal tumor and matched normal DNAs, 

 we found that certain cancers were excessively mutagenized by 

 human-specific L1s, while no verifiable insertions were 

 present in normal tissues. We confirmed de novo L1 insertions 

 in malignancy by both validating and sequencing 69/107 

 tumor-specific insertions and retrieving both 5' and 3' 

 junctions for 35. In contrast to germline polymorphic L1s, all 

 insertions were severely 5' truncated. Validated insertion 

 numbers varied from up to 17 in some tumors to none in three 

 others, and correlated with the age of the patients. Numerous 

 genes with a role in tumorigenesis were targeted, including 

 ODZ3, ROBO2, PTPRM, PCM1, and CDH11. Thus, somatic 

 retrotransposition may play an etiologic role in colorectal 

 cancer.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Groenen2012-st,

title = {Analyses of pig genomes provide insight into porcine 

 demography and evolution},

author = {Martien A M Groenen and Alan L Archibald and Hirohide Uenishi and Christopher K Tuggle and Yasuhiro Takeuchi and Max F Rothschild and Claire Rogel-Gaillard and Chankyu Park and Denis Milan and Hendrik-Jan Megens and Shengting Li and Denis M Larkin and Heebal Kim and Laurent A F Frantz and Mario Caccamo and Hyeonju Ahn and Bronwen L Aken and Anna Anselmo and Christian Anthon and Loretta Auvil and Bouabid Badaoui and Craig W Beattie and Christian Bendixen and Daniel Berman and Frank Blecha and Jonas Blomberg and Lars Bolund and Mirte Bosse and Sara Botti and Zhan Bujie and Megan Bystrom and Boris Capitanu and Denise Carvalho-Silva and Patrick Chardon and Celine Chen and Ryan Cheng and Sang-Haeng Choi and William Chow and Richard C Clark and Christopher Clee and Richard P M A Crooijmans and Harry D Dawson and Patrice Dehais and Fioravante De Sapio and Bert Dibbits and Nizar Drou and Zhi-Qiang Du and Kellye Eversole and Jo{~a}o Fadista and Susan Fairley and Thomas Faraut and Geoffrey J Faulkner and Katie E Fowler and Merete Fredholm and Eric Fritz and James G R Gilbert and Elisabetta Giuffra and Jan Gorodkin and Darren K Griffin and Jennifer L Harrow and Alexander Hayward and Kerstin Howe and Zhi-Liang Hu and Sean J Humphray and Toby Hunt and Henrik Hornsh{\o}j and Jin-Tae Jeon and Patric Jern and Matthew Jones and Jerzy Jurka and Hiroyuki Kanamori and Ronan Kapetanovic and Jaebum Kim and Jae-Hwan Kim and Kyu-Won Kim and Tae-Hun Kim and Greger Larson and Kyooyeol Lee and Kyung-Tai Lee and Richard Leggett and Harris A Lewin and Yingrui Li and Wansheng Liu and Jane E Loveland and Yao Lu and Joan K Lunney and Jian Ma and Ole Madsen and Katherine Mann and Lucy Matthews and Stuart McLaren and Takeya Morozumi and Michael P Murtaugh and Jitendra Narayan and Dinh Truong Nguyen and Peixiang Ni and Song-Jung Oh and Suneel Onteru and Frank Panitz and Eung-Woo Park and Hong-Seog Park and Geraldine Pascal and Yogesh Paudel and Miguel Perez-Enciso and Ricardo Ramirez-Gonzalez and James M Reecy and Sandra Rodriguez-Zas and Gary A Rohrer and Lauretta Rund and Yongming Sang and Kyle Schachtschneider and Joshua G Schraiber and John Schwartz and Linda Scobie and Carol Scott and Stephen Searle and Bertrand Servin and Bruce R Southey and Goran Sperber and Peter Stadler and Jonathan V Sweedler and Hakim Tafer and Bo Thomsen and Rashmi Wali and Jian Wang and Jun Wang and Simon White and Xun Xu and Martine Yerle and Guojie Zhang and Jianguo Zhang and Jie Zhang and Shuhong Zhao and Jane Rogers and Carol Churcher and Lawrence B Schook},

url = {http://dx.doi.org/10.1038/nature11622},

year  = {2012},

date = {2012-11-01},

journal = {Nature},

volume = {491},

number = {7424},

pages = {393--398},

abstract = {For 10,000 years pigs and humans have shared a close and 

 complex relationship. From domestication to modern breeding 

 practices, humans have shaped the genomes of domestic pigs. 

 Here we present the assembly and analysis of the genome 

 sequence of a female domestic Duroc pig (Sus scrofa) and a 

 comparison with the genomes of wild and domestic pigs from 

 Europe and Asia. Wild pigs emerged in South East Asia and 

 subsequently spread across Eurasia. Our results reveal a deep 

 phylogenetic split between European and Asian wild boars ∼1 

 million years ago, and a selective sweep analysis indicates 

 selection on genes involved in RNA processing and regulation. 

 Genes associated with immune response and olfaction exhibit 

 fast evolution. Pigs have the largest repertoire of functional 

 olfactory receptor genes, reflecting the importance of smell 

 in this scavenging animal. The pig genome sequence provides an 

 important resource for further improvements of this important 

 livestock species, and our identification of many putative 

 disease-causing variants extends the potential of the pig as a 

 biomedical model.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Plessy2012-qp,

title = {Promoter architecture of mouse olfactory receptor genes},

author = {Charles Plessy and Giovanni Pascarella and Nicolas Bertin and Altuna Akalin and Claudia Carrieri and Anne Vassalli and Dejan Lazarevic and Jessica Severin and Christina Vlachouli and Roberto Simone and Geoffrey J Faulkner and Jun Kawai and Carsten O Daub and Silvia Zucchelli and Yoshihide Hayashizaki and Peter Mombaerts and Boris Lenhard and Stefano Gustincich and Piero Carninci},

url = {http://dx.doi.org/10.1101/gr.126201.111},

year  = {2012},

date = {2012-03-01},

journal = {Genome Res.},

volume = {22},

number = {3},

pages = {486--497},

abstract = {Odorous chemicals are detected by the mouse main olfactory 

 epithelium (MOE) by about 1100 types of olfactory receptors 

 (OR) expressed by olfactory sensory neurons (OSNs). Each 

 mature OSN is thought to express only one allele of a single 

 OR gene. Major impediments to understand the transcriptional 

 control of OR gene expression are the lack of a proper 

 characterization of OR transcription start sites (TSSs) and 

 promoters, and of regulatory transcripts at OR loci. We have 

 applied the nanoCAGE technology to profile the transcriptome 

 and the active promoters in the MOE. nanoCAGE analysis 

 revealed the map and architecture of promoters for 87.5% of 

 the mouse OR genes, as well as the expression of many novel 

 noncoding RNAs including antisense transcripts. We identified 

 candidate transcription factors for OR gene expression and 

 among them confirmed by chromatin immunoprecipitation the 

 binding of TBP, EBF1 (OLF1), and MEF2A to OR promoters. 

 Finally, we showed that a short genomic fragment flanking the 

 major TSS of the OR gene Olfr160 (M72) can drive OSN-specific 

 expression in transgenic mice.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Schroder2012-yr,

title = {Conservation and divergence in Toll-like receptor 4-regulated 

 gene expression in primary human versus mouse macrophages},

author = {Kate Schroder and Katharine M Irvine and Martin S Taylor and Nilesh J Bokil and Kim-Anh Le Cao and Kelly-Anne Masterman and Larisa I Labzin and Colin A Semple and Ronan Kapetanovic and Lynsey Fairbairn and Altuna Akalin and Geoffrey J Faulkner and John Kenneth Baillie and Milena Gongora and Carsten O Daub and Hideya Kawaji and Geoffrey J McLachlan and Nick Goldman and Sean M Grimmond and Piero Carninci and Harukazu Suzuki and Yoshihide Hayashizaki and Boris Lenhard and David A Hume and Matthew J Sweet},

url = {http://dx.doi.org/10.1073/pnas.1110156109},

year  = {2012},

date = {2012-01-01},

journal = {Proc. Natl. Acad. Sci. U. S. A.},

volume = {109},

number = {16},

pages = {E944--53},

abstract = {Evolutionary change in gene expression is generally considered 

 to be a major driver of phenotypic differences between 

 species. We investigated innate immune diversification by 

 analyzing interspecies differences in the transcriptional 

 responses of primary human and mouse macrophages to the 

 Toll-like receptor (TLR)-4 agonist lipopolysaccharide (LPS). 

 By using a custom platform permitting cross-species 

 interrogation coupled with deep sequencing of mRNA 5' ends, we 

 identified extensive divergence in LPS-regulated orthologous 

 gene expression between humans and mice (24% of orthologues 

 were identified as ``divergently regulated''). We further 

 demonstrate concordant regulation of human-specific LPS target 

 genes in primary pig macrophages. Divergently regulated 

 orthologues were enriched for genes encoding cellular 

 ``inputs'' such as cell surface receptors (e.g., TLR6, 

 IL-7R$alpha$) and functional ``outputs'' such as inflammatory 

 cytokines/chemokines (e.g., CCL20, CXCL13). Conversely, 

 intracellular signaling components linking inputs to outputs 

 were typically concordantly regulated. Functional consequences 

 of divergent gene regulation were confirmed by showing LPS 

 pretreatment boosts subsequent TLR6 responses in mouse but not 

 human macrophages, in keeping with mouse-specific TLR6 

 induction. Divergently regulated genes were associated with a 

 large dynamic range of gene expression, and specific promoter 

 architectural features (TATA box enrichment, CpG island 

 depletion). Surprisingly, regulatory divergence was also 

 associated with enhanced interspecies promoter conservation. 

 Thus, the genes controlled by complex, highly conserved 

 promoters that facilitate dynamic regulation are also the most 

 susceptible to evolutionary change.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Upton2011-cl,

title = {Is somatic retrotransposition a parasitic or symbiotic 

 phenomenon?},

author = {Kyle R Upton and Kenneth J Baillie and Geoffrey J Faulkner},

url = {http://dx.doi.org/10.4161/mge.18422},

year  = {2011},

date = {2011-11-01},

journal = {Mob. Genet. Elements},

volume = {1},

number = {4},

pages = {279--282},

abstract = {The extraordinary evolutionary success of transposable 

 elements (TEs) invites us to question the nature of the 

 co-evolutionary dynamics between TE and host. Although 

 sometimes assumed to be wholly parasitic, TEs have penetrated 

 and spread throughout eukaryotic genomes at a rate 

 unparalleled by other parasites. This near-ubiquity, occurring 

 despite the potentially deleterious effects of insertional 

 mutagenesis, raises the possibility that a counterbalancing 

 benefit exists for the host. Such a benefit may act at the 

 population level to generate genomic diversity within a 

 species and hence greater adaptability under new selective 

 pressures, or at the level of primary gain for the individual. 

 Recent studies have highlighted the occurrence of 

 retrotransposition events in the germline and discovered a 

 surprisingly high rate of mobilization in somatic cells. Here 

 we examine the available evidence for somatic 

 retrotransposition and discuss how this phenomenon may confer 

 a selective advantage upon an individual or species.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Baillie2011-cw,

title = {Somatic retrotransposition alters the genetic landscape of the  human brain},

author = {Kenneth J Baillie and Mark W Barnett and Kyle R Upton and Daniel J Gerhardt and Todd A Richmond and Fioravante De Sapio and Paul M Brennan and Patrizia Rizzu and Sarah Smith and Mark Fell and Richard T Talbot and Stefano Gustincich and Thomas C Freeman and John S Mattick and David A Hume and Peter Heutink and Piero Carninci and Jeffrey A Jeddeloh and Geoffrey J Faulkner},

url = {http://dx.doi.org/10.1038/nature10531},

year  = {2011},

date = {2011-10-01},

journal = {Nature},

volume = {479},

number = {7374},

pages = {534--537},

abstract = {Retrotransposons are mobile genetic elements that use a 

 germline 'copy-and-paste' mechanism to spread throughout 

 metazoan genomes. At least 50 per cent of the human genome is 

 derived from retrotransposons, with three active families (L1, 

 Alu and SVA) associated with insertional mutagenesis and 

 disease. Epigenetic and post-transcriptional suppression block 

 retrotransposition in somatic cells, excluding early embryo 

 development and some malignancies. Recent reports of L1 

 expression and copy number variation in the human brain 

 suggest that L1 mobilization may also occur during later 

 development. However, the corresponding integration sites have 

 not been mapped. Here we apply a high-throughput method to 

 identify numerous L1, Alu and SVA germline mutations, as well 

 as 7,743 putative somatic L1 insertions, in the hippocampus 

 and caudate nucleus of three individuals. Surprisingly, we 

 also found 13,692 somatic Alu insertions and 1,350 SVA 

 insertions. Our results demonstrate that retrotransposons 

 mobilize to protein-coding genes differentially expressed and 

 active in the brain. Thus, somatic genome mosaicism driven by 

 retrotransposition may reshape the genetic circuitry that 

 underpins normal and abnormal neurobiological processes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Faulkner2011-hs,

title = {Retrotransposons: mobile and mutagenic from conception to 

 death},

author = {Geoffrey J Faulkner},

url = {http://dx.doi.org/10.1016/j.febslet.2011.03.061},

year  = {2011},

date = {2011-01-01},

journal = {FEBS Lett.},

volume = {585},

number = {11},

pages = {1589--1594},

abstract = {Mobile genetic elements feature prominently in mammalian 

 genome evolution. Several transposition-competent 

 retrotransposon families (L1, Alu, SVA) remain active in the 

 human germ line, leading to pathogenesis as well as genome 

 structural variation across the global population. 

 High-throughput screening approaches have recently been 

 developed to detect retrotransposon insertion polymorphisms. 

 Evidence produced by these and other genome-scale technologies 

 indicates an expanded role for retrotransposition in human 

 biology, including somatic mobilisation in the developing 

 embryo and in neural cells.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{De_Hoon2010-nt,

title = {Cross-mapping and the identification of editing sites in 

 mature microRNAs in high-throughput sequencing libraries},

author = {Michiel J L de Hoon and Ryan J Taft and Takehiro Hashimoto and Mutsumi Kanamori-Katayama and Hideya Kawaji and Mitsuoki Kawano and Mami Kishima and Timo Lassmann and Geoffrey J Faulkner and John S Mattick and Carsten O Daub and Piero Carninci and Jun Kawai and Harukazu Suzuki and Yoshihide Hayashizaki},

url = {http://dx.doi.org/10.1101/gr.095273.109},

year  = {2010},

date = {2010-02-01},

journal = {Genome Res.},

volume = {20},

number = {2},

pages = {257--264},

abstract = {MicroRNAs (miRNAs) are short (20-23 nt) RNAs that are 

 sequence-specific mediators of transcriptional and 

 post-transcriptional regulation of gene expression. Modern 

 high-throughput technologies enable deep sequencing of such 

 RNA species on an unprecedented scale. We find that the 

 analysis of small RNA deep-sequencing libraries can be 

 affected by cross-mapping, in which RNA sequences originating 

 from one locus are inadvertently mapped to another. Similar to 

 cross-hybridization on microarrays, cross-mapping is prevalent 

 among miRNAs, as they tend to occur in families, are similar 

 or derived from repeat or structural RNAs, or are 

 post-transcriptionally modified. Here, we develop a strategy 

 to correct for cross-mapping, and apply it to the analysis of 

 RNA editing in mature miRNAs. In contrast to previous reports, 

 our analysis suggests that RNA editing in mature miRNAs is 

 rare in animals.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Mattick2010-dl,

title = {A global view of genomic information--moving beyond the gene 

 and the master regulator},

author = {John S Mattick and Ryan J Taft and Geoffrey J Faulkner},

url = {http://dx.doi.org/10.1016/j.tig.2009.11.002},

year  = {2010},

date = {2010-01-01},

journal = {Trends Genet.},

volume = {26},

number = {1},

pages = {21--28},

abstract = {The current view of gene regulation in complex organisms holds 

 that gene expression is largely controlled by the combinatoric 

 actions of transcription factors and other regulatory 

 proteins, some of which powerfully influence cell type. Recent 

 large-scale studies have confirmed that cellular 

 differentiation involves many different regulatory factors. 

 However, other studies indicate that the genome is pervasively 

 transcribed to produce a variety of short and long 

 non-protein-coding RNAs, including those derived from 

 retrotransposed sequences, which also play important roles in 

 the epigenetic regulation of gene expression. The evidence 

 suggests that ontogenesis requires interplay between 

 state-specific regulatory proteins, multitasked effector 

 complexes and target-specific RNAs that recruit these 

 complexes to their sites of action. Moreover, the 

 semi-continuous nature of the transcriptome prompts the 

 reassessment of 'genes' as discrete entities and indicates 

 that the mammalian genome might be more accurately viewed as 

 islands of protein-coding information in a sea of cis- and 

 trans-acting regulatory sequences.},

keywords = {},

pubstate = {},

tppubtype = {article}

}

@article{Cloonan2009-qj,

title = {RNA-MATE: a recursive mapping strategy for high-throughput 

 RNA-sequencing data},

author = {Nicole Cloonan and Qinying Xu and Geoffrey J Faulkner and Darrin F Taylor and Dave T P Tang and Gabriel Kolle and Sean M Grimmond},

url = {http://dx.doi.org/10.1093/bioinformatics/btp459},

year  = {2009},

date = {2009-10-01},

journal = {Bioinformatics},

volume = {25},

number = {19},

pages = {2615--2616},

abstract = {UNLABELLED: Mapping of next-generation sequencing data derived 

 from RNA samples (RNAseq) presents different genome mapping 

 challenges than data derived from DNA. For example, tags that 

 cross exon-junction boundaries will often not map to a 

 reference genome, and the strand specificity of the data needs 

 to be retained. Here we present RNA-MATE, a computational 

 pipeline based on a recursive mapping strategy for placing 

 strand specific RNAseq data onto a reference genome. 

 Maximizing the mappable tags can provide significant savings 

 in the cost of sequencing experiments. This pipeline provides 

 an automatic and integrated way to align color-space 

 sequencing data, collate this information and generate files 

 for examining gene-expression data in a genomic context. 

 AVAILABILITY: Executables, source code, and exon-junction 

 libraries are available from 

 http://grimmond.imb.uq.edu.au/RNA-MATE/},

keywords = {},

pubstate = {},

tppubtype = {article}

}