@article{e6716d200bab4b94b34db83955f1211d,
title = "DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape",
abstract = "Transposable element (TE)-derived sequences comprise half of the human genome and DNA methylome and are presumed to be densely methylated and inactive. Examination of genome-wide DNA methylation status within 928 TE subfamilies in human embryonic and adult tissues identified unexpected tissue-specific and subfamily-specific hypomethylation signatures. Genes proximal to tissue-specific hypomethylated TE sequences were enriched for functions important for the relevant tissue type, and their expression correlated strongly with hypomethylation within the TEs. When hypomethylated, these TE sequences gained tissue-specific enhancer marks, including monomethylation of histone H3 at lysine 4 (H3K4me1) and occupancy by p300, and a majority exhibited enhancer activity in reporter gene assays. Many such TEs also harbored binding sites for transcription factors that are important for tissue-specific functions and showed evidence of evolutionary selection. These data suggest that sequences derived from TEs may be responsible for wiring tissue type-specific regulatory networks and may have acquired tissue-specific epigenetic regulation.",
author = "Mingchao Xie and Chibo Hong and Bo Zhang and Lowdon, {Rebecca F.} and Xiaoyun Xing and Daofeng Li and Xin Zhou and Lee, {Hyung Joo} and Maire, {Cecile L.} and Ligon, {Keith L.} and Philippe Gascard and Mahvash Sigaroudinia and Tlsty, {Thea D.} and Theresa Kadlecek and Arthur Weiss and Henriette O'Geen and Farnham, {Peggy J.} and Madden, {Pamela A.F.} and Mungall, {Andrew J.} and Angela Tam and Baljit Kamoh and Stephanie Cho and Richard Moore and Martin Hirst and Marra, {Marco A.} and Costello, {Joseph F.} and Ting Wang",
note = "Funding Information: computing environment. We thank the UCSC Genome Browser bioinformatics team for providing processed ENCODE data. We acknowledge support from the US National Institutes of Health (NIH) Roadmap Epigenomics Program, sponsored by the National Institute on Drug Abuse (NIDA) and the National Institute of Environmental Health Sciences (NIEHS). J.F.C., T.W., P.J.F. and M.H. are supported by US NIH grant 5U01ES017154. B.Z. and X.Z. are supported by the NIDA R25 program DA027995. K.L.L. and C.L.M. are supported by US NIH grants P01CA095616 and P01CA142536. T.W. is supported in part by the March of Dimes Foundation, the Edward Mallinckrodt Jr. Foundation, US NIH grant P50CA134254 and a generous start-up package from the Department of Genetics at the Washington University School of Medicine.",
year = "2013",
month = jul,
doi = "10.1038/ng.2649",
language = "English",
volume = "45",
pages = "836--841",
journal = "Nature Genetics",
issn = "1061-4036",
number = "7",
}