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.
authors.affiliation: Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Mingchao
authors.initials: M
authors.lastname: Xie
authors.forename: Chibo
authors.initials: C
authors.lastname: Hong
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: Lowdon
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Xing
authors.forename: Daofeng
authors.initials: D
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Hyung Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Cecile L
authors.initials: CL
authors.lastname: Maire
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.forename: Philippe
authors.initials: P
authors.lastname: Gascard
authors.forename: Mahvash
authors.initials: M
authors.lastname: Sigaroudinia
authors.forename: Thea D
authors.initials: TD
authors.lastname: Tlsty
authors.forename: Theresa
authors.initials: T
authors.lastname: Kadlecek
authors.forename: Arthur
authors.initials: A
authors.lastname: Weiss
authors.forename: Henriette
authors.initials: H
authors.lastname: O'Geen
authors.forename: Peggy J
authors.initials: PJ
authors.lastname: Farnham
authors.forename: Pamela A F
authors.initials: PA
authors.lastname: Madden
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mungall
authors.forename: Angela
authors.initials: A
authors.lastname: Tam
authors.forename: Baljit
authors.initials: B
authors.lastname: Kamoh
authors.forename: Stephanie
authors.initials: S
authors.lastname: Cho
authors.forename: Richard
authors.initials: R
authors.lastname: Moore
authors.forename: Martin
authors.initials: M
authors.lastname: Hirst
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Costello
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
mesh_terms: D000328:Adult; D001665:Binding Sites / Q000235:genetics; D002478:Cells, Cultured; D002874:Chromosome Mapping; D019175:DNA Methylation; D004251:DNA Transposable Elements / Q000235:genetics*; D004622:Embryo, Mammalian; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D044127:Epigenesis, Genetic; D015894:Genome, Human; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D005810:Multigene Family / Q000235:genetics*; D009928:Organ Specificity / Q000235:genetics
chemical_list: D004251:DNA Transposable Elements; D006657:Histones