Francisco J Sanchez-Luque, Marie-Jeanne H C Kempen, Patricia Gerdes, Dulce B Vargas-Landin, Sandra R Richardson, Robin-Lee Troskie, Samuel J Jesuadian, Seth W Cheetham, Patricia E Carreira, Carmen Salvador-Palomeque, Marta García-Cañadas, Martin Muñoz-Lopez, Laura Sanchez, Mischa Lundberg, Angela Macia, Sara R Heras, Paul M Brennan, Ryan Lister, Jose L Garcia-Perez, Adam D Ewing, Geoffrey J Faulkner: LINE-1 Evasion of Epigenetic Repression in Humans. In: Molecular Cell, 0 (0), 2019, ISSN: 1097-2765.

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

BibTeX (Download)

@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 = {Faulknerlab, Major_Publication},
pubstate = {published},
tppubtype = {article}
}