Xie, MingchaoHong, ChiboZhang, BoLowdon, RebeccaXing, XiaoyunLi, DaofengZhou, XinLee, Hyung JooMaire, Cecile L.Ligon, KeithGascard, PhilippeSigaroudinia, MahvashTlsty, Thea D.Kadlecek, TheresaWeiss, ArthurO’Geen, HenrietteFarnham, Peggy J.Madden, Pamela A.F.Mungall, Andrew J.Tam, AngelaKamoh, BaljitCho, StephanieMoore, RichardHirst, MartinMarra, Marco A.Costello, Joseph F.Wang, Ting2014-03-112013Xie, M., C. Hong, B. Zhang, R. Lowdon, X. Xing, D. Li, X. Zhou, et al. 2013. “DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape.” Nature genetics 45 (7): 10.1038/ng.2649. doi:10.1038/ng.2649. http://dx.doi.org/10.1038/ng.2649.1061-4036http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879711Introduction: Transposable element (TE) derived sequences comprise half of our genome and DNA methylome, and are presumed densely methylated and inactive. Examination of the genome-wide DNA methylation status within 928 TE subfamilies in human embryonic and adult tissues revealed unexpected tissue-specific and subfamily-specific hypomethylation signatures. Genes proximal to tissue-specific hypomethylated TE sequences were enriched for functions important for the tissue type and their expression correlated strongly with hypomethylation of the TEs. When hypomethylated, these TE sequences gained tissue-specific enhancer marks including 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 exhibited evidence for evolutionary selection. These data suggest that sequences derived from TEs may be responsible for wiring tissue type-specific regulatory networks, and have acquired tissue-specific epigenetic regulation.en-USJournal Article2014-03-1110.1038/ng.2649