title: Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors.
abstract: Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) has become the dominant technique for mapping transcription factor (TF) binding regions genome-wide. We performed an integrative analysis centered around 457 ChIP-seq data sets on 119 human TFs generated by the ENCODE Consortium. We identified highly enriched sequence motifs in most data sets, revealing new motifs and validating known ones. The motif sites (TF binding sites) are highly conserved evolutionarily and show distinct footprints upon DNase I digestion. We frequently detected secondary motifs in addition to the canonical motifs of the TFs, indicating tethered binding and cobinding between multiple TFs. We observed significant position and orientation preferences between many cobinding TFs. Genes specifically expressed in a cell line are often associated with a greater occurrence of nearby TF binding in that cell line. We observed cell-line-specific secondary motifs that mediate the binding of the histone deacetylase HDAC2 and the enhancer-binding protein EP300. TF binding sites are located in GC-rich, nucleosome-depleted, and DNase I sensitive regions, flanked by well-positioned nucleosomes, and many of these features show cell type specificity. The GC-richness may be beneficial for regulating TF binding because, when unoccupied by a TF, these regions are occupied by nucleosomes in vivo. We present the results of our analysis in a TF-centric web repository Factorbook (http://factorbook.org) and will continually update this repository as more ENCODE data are generated.
authors.affiliation: Program in Bioinformatics and Integrative Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Jiali
authors.initials: J
authors.lastname: Zhuang
authors.forename: Sowmya
authors.initials: S
authors.lastname: Iyer
authors.forename: XinYing
authors.initials: X
authors.lastname: Lin
authors.forename: Troy W
authors.initials: TW
authors.lastname: Whitfield
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Greven
authors.forename: Brian G
authors.initials: BG
authors.lastname: Pierce
authors.forename: Xianjun
authors.initials: X
authors.lastname: Dong
authors.forename: Anshul
authors.initials: A
authors.lastname: Kundaje
authors.forename: Yong
authors.initials: Y
authors.lastname: Cheng
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Rando
authors.forename: Ewan
authors.initials: E
authors.lastname: Birney
authors.forename: Richard M
authors.initials: RM
authors.lastname: Myers
authors.forename: William S
authors.initials: WS
authors.lastname: Noble
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Weng
mesh_terms: D001482:Base Composition; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D003850:Deoxyribonuclease I / Q000378:metabolism; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020407:Internet; D058977:Molecular Sequence Annotation; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D059372:Nucleotide Motifs; D009928:Organ Specificity / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D009707:Nucleosomes; D014157:Transcription Factors; D003850:Deoxyribonuclease I