title: Open chromatin defined by DNaseI and FAIRE identifies regulatory elements that shape cell-type identity.
abstract: The human body contains thousands of unique cell types, each with specialized functions. Cell identity is governed in large part by gene transcription programs, which are determined by regulatory elements encoded in DNA. To identify regulatory elements active in seven cell lines representative of diverse human cell types, we used DNase-seq and FAIRE-seq (Formaldehyde Assisted Isolation of Regulatory Elements) to map "open chromatin." Over 870,000 DNaseI or FAIRE sites, which correspond tightly to nucleosome-depleted regions, were identified across the seven cell lines, covering nearly 9% of the genome. The combination of DNaseI and FAIRE is more effective than either assay alone in identifying likely regulatory elements, as judged by coincidence with transcription factor binding locations determined in the same cells. Open chromatin common to all seven cell types tended to be at or near transcription start sites and to be coincident with CTCF binding sites, while open chromatin sites found in only one cell type were typically located away from transcription start sites and contained DNA motifs recognized by regulators of cell-type identity. We show that open chromatin regions bound by CTCF are potent insulators. We identified clusters of open regulatory elements (COREs) that were physically near each other and whose appearance was coordinated among one or more cell types. Gene expression and RNA Pol II binding data support the hypothesis that COREs control gene activity required for the maintenance of cell-type identity. This publicly available atlas of regulatory elements may prove valuable in identifying noncoding DNA sequence variants that are causally linked to human disease.
authors.affiliation: Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Song
authors.forename: Zhancheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Linda L
authors.initials: LL
authors.lastname: Grasfeder
authors.forename: Alan P
authors.initials: AP
authors.lastname: Boyle
authors.forename: Paul G
authors.initials: PG
authors.lastname: Giresi
authors.forename: Bum-Kyu
authors.initials: BK
authors.lastname: Lee
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Sheffield
authors.forename: Stefan
authors.initials: S
authors.lastname: Gräf
authors.forename: Mikael
authors.initials: M
authors.lastname: Huss
authors.forename: Damian
authors.initials: D
authors.lastname: Keefe
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Darin
authors.initials: D
authors.lastname: London
authors.forename: Ryan M
authors.initials: RM
authors.lastname: McDaniell
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Shibata
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Showers
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Simon
authors.forename: Teresa
authors.initials: T
authors.lastname: Vales
authors.forename: Tianyuan
authors.initials: T
authors.lastname: Wang
authors.forename: Deborah
authors.initials: D
authors.lastname: Winter
authors.forename: Zhuzhu
authors.initials: Z
authors.lastname: Zhang
authors.forename: Neil D
authors.initials: ND
authors.lastname: Clarke
authors.forename: Ewan
authors.initials: E
authors.lastname: Birney
authors.forename: Vishwanath R
authors.initials: VR
authors.lastname: Iyer
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Crawford
authors.forename: Jason D
authors.initials: JD
authors.lastname: Lieb
authors.forename: Terrence S
authors.initials: TS
authors.lastname: Furey
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D002874:Chromosome Mapping; D005786:Gene Expression Regulation; D006801:Humans; D011485:Protein Binding; D050436:Regulatory Elements, Transcriptional; D012097:Repressor Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA / Q000379:methods*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002843:Chromatin; D012097:Repressor Proteins