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.

Selective Roles for cAMP Response Element-binding Protein Binding Protein and p300 Protein as Coregulators for Androgen-regulated Gene Expression in Advanced Prostate Cancer Cells

“…Other investigators have also observed a critical role for p300 in ADI prostate cancer cells (6). In addition, a genome-wide ChIP analysis of p300 and CBP in glioblastoma cells revealed that the majority of genes that were regulated by serum addition were bound preferentially by p300 rather than CBP (39).…”

“…Although the differential requirement for p300 in this case was not due to differential recruitment of p300, the mechanism responsible for the differential requirement presumably lies in some different aspect of promoter environment at the two genes. As suggested by Ramos et al (39), differences in binding sites for other transcription factors near the ARE could influence whether p300 or CBP is recruited. In addition, differences in the DNA sequence at steroid receptor binding sites can lead to altered conformations of the DNAbound steroid receptor, resulting in recruitment of different sets of coactivators (40 -43).…”

“…Ramos et al (39) found that genes which were preferentially bound by either CBP or p300 also exhibited differences in the enrichment of other transcription factor binding sites associated with either p300-specific or CBP-specific targets (39). Thus, the presence of specific transcription factors in the promoter environment may favor recruitment of either p300 or CBP, perhaps because of preferential interactions of various transcription factors with either p300 or CBP.…”

Bayesian analysis for mixtures of discrete distributions with a non-parametric component

“…In this paper, we use for illustration the ChIP-Seq data generated by Ramos et al (2010) for identifying the genomic regions bound by the histone acetyltransferases p300.…”

“…Table 1 provides the summary statistics for the data set, where we consider only the data for 1000bp windows along chromosome 21 (Bao et al, 2013). Figure 1 shows Ramos et al (2010) for one experiment on the protein p300 on chromosome21.…”