The double bromodomain proteins Brd2 and Brd3 couple histone acetylation to transcription
The double bromodomain proteins Brd2 and Brd3 couple histone acetylation to transcription
复制标题
DOI：
10.1016/j.molcel.2008.01.018
复制
发表时间：
2008-04-11
期刊：
影响因子：
16
通讯作者：
Flint, S. J.
中科院分区：
文献类型：
--
作者：
LeRoy, Gary;Rickards, Brenden;Flint, S. J.
翻译后的组蛋白修饰对于染色质结构的调节和转录的调节至关重要。存在于许多染色质相关蛋白中的溴结构域识别乙酰化赖氨酸；在组蛋白的非结构化N-末端区域。在这里，我们报告了双溴结构域蛋白Brd2和Brd3在体内优先与转录基因全长上的高乙酰化染色质相关联。Brd2和Brd3相关的染色质显著富含H4K5、H4K12和H3K14乙酰化，并含有相对较少的二甲基化H3K9。Brd2和Brd3都允许RNA聚合酶11在特定的转录系统中通过核小体进行转录。这种活性依赖于已知的被Brd蛋白识别的特定的组蛋白H4修饰。我们还证明了Brd2具有内在的组蛋白伴侣活性，是细胞周期蛋白D1基因在体内转录所必需的。这些数据确定了使以乙酰化标记的核小体允许延伸的RNA聚合酶II通过的蛋白质。
Posttranslational histone modifications are crucial for the modulation of chromatin structure and regulation of transcription. Bromodomains present in many chromatin-associated proteins recognize acetylated lysines; in the unstructured N-terminal regions of histones. Here, we report that the double bromodomain proteins Brd2 and Brd3 associate preferentially in vivo with hyperacetylated chromatin along the entire lengths of transcribed genes. Brd2- and Brd3-associated chromatin is significantly enriched in H4K5, H4K12, and H3K14 acetylation and contains relatively little dimethylated H3K9. Both Brd2 and Brd3 allowed RNA polymerase 11 to transcribe through nucleosomes; in a defined transcription system. Such activity depended on specific histone H4 modifications known to be recognized by the Brd proteins. We also demonstrate that Brd2 has intrinsic histone chaperone activity and is required for transcription of the cyclin D1 gene in vivo. These data identify proteins that render nucleosomes marked by acetylation permissive to the passage of elongating RNA polymerase II.