title: High-resolution genome-wide in vivo footprinting of diverse transcription factors in human cells.
abstract: Regulation of gene transcription in diverse cell types is determined largely by varied sets of cis-elements where transcription factors bind. Here we demonstrate that data from a single high-throughput DNase I hypersensitivity assay can delineate hundreds of thousands of base-pair resolution in vivo footprints in human cells that precisely mark individual transcription factor-DNA interactions. These annotations provide a unique resource for the investigation of cis-regulatory elements. We find that footprints for specific transcription factors correlate with ChIP-seq enrichment and can accurately identify functional versus nonfunctional transcription factor motifs. We also find that footprints reveal a unique evolutionary conservation pattern that differentiates functional footprinted bases from surrounding DNA. Finally, detailed analysis of CTCF footprints suggests multiple modes of binding and a novel DNA binding motif upstream of the primary binding site.
authors.affiliation: Institute for Genome Sciences & Policy, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Boyle
authors.forename: Lingyun
authors.initials: L
authors.lastname: Song
authors.forename: Bum-Kyu
authors.initials: BK
authors.lastname: Lee
authors.forename: Darin
authors.initials: D
authors.lastname: London
authors.forename: Damian
authors.initials: D
authors.lastname: Keefe
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: Terrence S
authors.initials: TS
authors.lastname: Furey
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism; D016678:Genome; D023281:Genomics; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D023302:Protein Footprinting / Q000379:methods*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; D004247:DNA; D003850:Deoxyribonuclease I