Carmen Salvador-Palomeque

@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{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{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}

}