在基因激活过程中，EP400将H3.3沉积到启动子和增强子中。
EP400 Deposits H3.3 into Promoters and Enhancers during Gene Activation.
作者信息
Pradhan Suman K, Su Trent, Yen Linda, Jacquet Karine, Huang Chengyang, Côté Jacques, Kurdistani Siavash K, Carey Michael F
机构信息
Department of Biological Chemistry, David Geffen School of Medicine, UCLA, 351A Biomedical Sciences Research Building, 615 Charles E. Young Drive South, Los Angeles, CA 90095-1737, USA.
The Molecular Biology Institute, UCLA, Paul D. Boyer Hall, 611 Charles E. Young Drive South, Los Angeles, CA 90095-1570, USA.
出版信息
Mol Cell. 2016 Jan 7;61(1):27-38. doi: 10.1016/j.molcel.2015.10.039. Epub 2015 Dec 6.
Gene activation in metazoans is accompanied by the presence of histone variants H2AZ and H3.3 within promoters and enhancers. It is not known, however, what protein deposits H3.3 into chromatin or whether variant chromatin plays a direct role in gene activation. Here we show that chromatin containing acetylated H2AZ and H3.3 stimulates transcription in vitro. Analysis of the Pol II pre-initiation complex on immobilized chromatin templates revealed that the E1A binding protein p400 (EP400) was bound preferentially to and required for transcription stimulation by acetylated double-variant chromatin. EP400 also stimulated H2AZ/H3.3 deposition into promoters and enhancers and influenced transcription in vivo at a step downstream of the Mediator complex. EP400 efficiently exchanged recombinant histones H2A and H3.1 with H2AZ and H3.3, respectively, in a chromatin- and ATP-stimulated manner in vitro. Our data reveal that EP400 deposits H3.3 into chromatin alongside H2AZ and contributes to gene regulation after PIC assembly.
后生动物中的基因激活伴随着启动子和增强子区域存在组蛋白变体H2AZ和H3.3。然而，尚不清楚是什么蛋白质将H3.3沉积到染色质中，也不清楚变体染色质是否在基因激活中起直接作用。在这里，我们表明含有乙酰化H2AZ和H3.3的染色质在体外刺激转录。对固定染色质模板上的Pol II预起始复合物的分析表明，E1A结合蛋白p400（EP400）优先结合乙酰化双变体染色质并对其转录刺激是必需的。EP400还刺激H2AZ/H3.3沉积到启动子和增强子中，并在体内中介复合物下游的步骤影响转录。在体外，EP400能以染色质和ATP刺激的方式分别有效地将重组组蛋白H2A和H3.1与H2AZ和H3.3进行交换。我们的数据表明，EP400与H2AZ一起将H3.3沉积到染色质中，并在预起始复合物组装后对基因调控起作用。
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