DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape
Lee, Hyung Joo
Maire, Cecile L.
Tlsty, Thea D.
Farnham, Peggy J.
Madden, Pamela A.F.
Mungall, Andrew J.
Marra, Marco A.
Costello, Joseph F.
Wang, TingNote: Order does not necessarily reflect citation order of authors.
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CitationXie, 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.
AbstractIntroduction: 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.
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