Patricia Gerdes

@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{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{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{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{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{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}

}