Genome-wide assessment of differential roles for p300 and CBP in transcription regulation.

Genome-wide assessment of differential roles for p300 and CBP in transcription regulation.
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DOI:
10.1093/nar/gkq184
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发表时间:
2010-09
影响因子:
14.9
通讯作者:
't Hoen PA
't Hoen PA
中科院分区:
生物学2区
文献类型:
--
作者:
Ramos YF;Hestand MS;Verlaan M;Krabbendam E;Ariyurek Y;van Galen M;van Dam H;van Ommen GJ;den Dunnen JT;Zantema A;'t Hoen PA

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尽管同源性很高,但转录共激活因子p300和CREB结合蛋白(CBP)在胚胎发育过程中都是不可或缺的。众所周知,它们调控的是相同的基因。为了确定优先受p300或CBP调控的基因,我们使用细胞周期同步细胞芯片序列进行了广泛的全基因组调查。我们发现,57%的标签位于基因或近端启动子内,总体上倾向于与转录起始和结束位点结合。这种不同的结合模式可能反映了CBP和p300在转录调控中的不同作用。16103个基因中的大多数都被CBP和p300结合。然而,刺激后,89和1944个基因分别优先与CBP或p300结合。研究发现,靶基因主要参与代谢和发育过程的调节以及转录,CBP对转录负调控的基因表现出比p300更强的偏好。转录因子结合位点分析表明,CBP和p300有许多共同的伙伴,但AP-1和血清反应因子(SRF)似乎在CBP特异序列中更突出,而AP-2和SP1富含p300特异靶标。综上所述,我们的发现进一步阐明了辅助激活因子p300和CBP在转录调控中的不同作用。
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.
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