RNA Binding to CBP Stimulates Histone Acetylation and Transcription.
RNA Binding to CBP Stimulates Histone Acetylation and Transcription.
复制标题
DOI：
10.1016/j.cell.2016.12.020
复制
发表时间：
2017-01-12
期刊：
影响因子：
64.5
通讯作者：
Berger SL
中科院分区：
文献类型：
--
作者：
Bose DA;Donahue G;Reinberg D;Shiekhattar R;Bonasio R;Berger SL
CBP/p300是转录共激活因子，其结合是增强子的特征，增强子是控制多细胞生物体中基因表达模式的顺式调节元件。活性增强子产生双向增强子RNA（eRNA）并显示CBP/p300依赖性组蛋白乙酰化。在这里，我们证明CBP直接结合RNA在体内和体外。体内结合CBP的RNA包括大量eRNA。使用稳态组蛋白乙酰转移酶（HAT）测定，我们表明，CBP的HAT结构域中的RNA结合区-CBP/p300独特的调控基序-允许RNA刺激CBP的HAT活性。在CBP与eRNA相互作用的增强子处，刺激表现为CBP介导的组蛋白乙酰化的RNA依赖性变化，如H3 K27 ac，以及基因表达的相应变化。通过直接与CBP相互作用，eRNA有助于在活性增强子处形成独特的染色质结构，这反过来又是调节靶基因所必需的。
CBP/p300 are transcription co-activators whose binding is a signature of enhancers, cis-regulatory elements that control patterns of gene expression in multicellular organisms. Active enhancers produce bi-directional enhancer RNAs (eRNAs) and display CBP/p300 dependent histone acetylation. Here, we demonstrate that CBP binds directly to RNAs in vivo and in vitro. RNAs bound to CBP in vivo include a large number of eRNAs. Using steady-state histone acetyltransferase (HAT) assays we show that an RNA binding region in the HAT domain of CBP— a regulatory motif unique to CBP/p300—allows RNA to stimulate CBP’s HAT activity. At enhancers where CBP interacts with eRNAs, stimulation manifests in RNA-dependent changes in the histone acetylation mediated by CBP, such as H3K27ac, and by corresponding changes in gene expression. By interacting directly with CBP, eRNAs contribute to the unique chromatin structure at active enhancers, which in turn is required for regulation of target genes.