title: Genome-wide assessment of differential roles for p300 and CBP in transcription regulation.
abstract: Despite high levels of homology, transcription coactivators p300 and CREB binding protein (CBP) are both indispensable during embryogenesis. They are largely known to regulate the same genes. To identify genes preferentially regulated by p300 or CBP, we performed an extensive genome-wide survey using the ChIP-seq on cell-cycle synchronized cells. We found that 57% of the tags were within genes or proximal promoters, with an overall preference for binding to transcription start and end sites. The heterogeneous binding patterns possibly reflect the divergent roles of CBP and p300 in transcriptional regulation. Most of the 16 103 genes were bound by both CBP and p300. However, after stimulation 89 and 1944 genes were preferentially bound by CBP or p300, respectively. Target genes were found to be primarily involved in the regulation of metabolic and developmental processes, and transcription, with CBP showing a stronger preference than p300 for genes active in negative regulation of transcription. Analysis of transcription factor binding sites suggest that CBP and p300 have many partners in common, but AP-1 and Serum Response Factor (SRF) appear to be more prominent in CBP-specific sequences, whereas AP-2 and SP1 are enriched in p300-specific targets. Taken together, our findings further elucidate the distinct roles of coactivators p300 and CBP in transcriptional regulation.
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Postzone S4-0P, PO Box 9600, 2300 RC Leiden, The Netherlands. y.f.m.ramos@lumc.nl
authors.forename: Yolande F M
authors.initials: YF
authors.lastname: Ramos
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Hestand
authors.forename: Matty
authors.initials: M
authors.lastname: Verlaan
authors.forename: Elise
authors.initials: E
authors.lastname: Krabbendam
authors.forename: Yavuz
authors.initials: Y
authors.lastname: Ariyurek
authors.forename: Michiel
authors.initials: M
authors.lastname: van Galen
authors.forename: Hans
authors.initials: H
authors.lastname: van Dam
authors.forename: Gert-Jan B
authors.initials: GJ
authors.lastname: van Ommen
authors.forename: Johan T
authors.initials: JT
authors.lastname: den Dunnen
authors.forename: Alt
authors.initials: A
authors.lastname: Zantema
authors.forename: Peter A C
authors.initials: PA
authors.lastname: 't Hoen
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D050882:CREB-Binding Protein / Q000378:metabolism*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D016384:Consensus Sequence; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D011401:Promoter Regions, Genetic; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
chemical_list: D050882:CREB-Binding Protein; D050881:E1A-Associated p300 Protein