title: Cell-type specific and combinatorial usage of diverse transcription factors revealed by genome-wide binding studies in multiple human cells.
abstract: Cell-type diversity is governed in part by differential gene expression programs mediated by transcription factor (TF) binding. However, there are few systematic studies of the genomic binding of different types of TFs across a wide range of human cell types, especially in relation to gene expression. In the ENCODE Project, we have identified the genomic binding locations across 11 different human cell types of CTCF, RNA Pol II (RNAPII), and MYC, three TFs with diverse roles. Our data and analysis revealed how these factors bind in relation to genomic features and shape gene expression and cell-type specificity. CTCF bound predominantly in intergenic regions while RNAPII and MYC preferentially bound to core promoter regions. CTCF sites were relatively invariant across diverse cell types, while MYC showed the greatest cell-type specificity. MYC and RNAPII co-localized at many of their binding sites and putative target genes. Cell-type specific binding sites, in particular for MYC and RNAPII, were associated with cell-type specific functions. Patterns of binding in relation to gene features were generally conserved across different cell types. RNAPII occupancy was higher over exons than adjacent introns, likely reflecting a link between transcriptional elongation and splicing. TF binding was positively correlated with the expression levels of their putative target genes, but combinatorial binding, in particular of MYC and RNAPII, was even more strongly associated with higher gene expression. These data illuminate how combinatorial binding of transcription factors in diverse cell types is associated with gene expression and cell-type specific biology.
authors.affiliation: Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, Texas 78712, USA.
authors.forename: Bum-Kyu
authors.initials: BK
authors.lastname: Lee
authors.forename: Akshay A
authors.initials: AA
authors.lastname: Bhinge
authors.forename: Anna
authors.initials: A
authors.lastname: Battenhouse
authors.forename: Ryan M
authors.initials: RM
authors.lastname: McDaniell
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Lingyun
authors.initials: L
authors.lastname: Song
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Ni
authors.forename: Ewan
authors.initials: E
authors.lastname: Birney
authors.forename: Jason D
authors.initials: JD
authors.lastname: Lieb
authors.forename: Terrence S
authors.initials: TS
authors.lastname: Furey
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Crawford
authors.forename: Vishwanath R
authors.initials: VR
authors.lastname: Iyer
mesh_terms: D005786:Gene Expression Regulation / Q000502:physiology*; D015894:Genome, Human / Q000502:physiology*; D055106:Genome-Wide Association Study / Q000379:methods; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D020014:K562 Cells; D009928:Organ Specificity / Q000502:physiology; D012319:RNA Polymerase II / Q000378:metabolism*; D012326:RNA Splicing / Q000502:physiology; D020218:Response Elements / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D014157:Transcription Factors; D012319:RNA Polymerase II
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