BRD4 is a histone acetyltransferase that evicts nucleosomes from chromatin.
BRD4 is a histone acetyltransferase that evicts nucleosomes from chromatin.
复制标题
DOI：
10.1038/nsmb.3228
复制
发表时间：
2016-06
影响因子：
16.8
通讯作者：
Singer DS
中科院分区：
文献类型：
--
作者：
Devaiah BN;Case-Borden C;Gegonne A;Hsu CH;Chen Q;Meerzaman D;Dey A;Ozato K;Singer DS
溴结构域蛋白4（BRD4）是与癌症和自身免疫性疾病有关的染色质结合蛋白，其在启动子和超级增强子处充当转录因子的支架。尽管染色质去致密化和靶基因的转录激活与BRD4结合相关，但所涉及的机制尚不清楚。我们报告，BRD4是一种新的组蛋白乙酰转移酶（HAT），乙酰化组蛋白H3和H4的模式不同于其他HAT的。小鼠和人BRD 4均表现出固有的HAT活性。重要的是，BRD4乙酰化H3K122，这是核小体稳定性的关键残基，导致核小体驱逐和染色质去致密化。BRD 4的核小体清除发生在全基因组范围内，包括在其靶MYC、FOS和AURKB（极光B激酶）处，导致转录增加。由于BRD4调节转录，这些发现导致BRD4主动连接染色质结构和转录的模型：它通过乙酰化和驱逐靶基因的核小体介导染色质去致密化，从而激活它们的转录。
Bromodomain protein 4 (BRD4) is a chromatin-binding protein implicated in cancer and autoimmune diseases that functions as a scaffold for transcription factors at promoters and super-enhancers. Whereas chromatin de-compaction and transcriptional activation of target genes are associated with BRD4 binding, the mechanism(s) involved are unknown. We report that BRD4 is a novel histone acetyltransferase (HAT) that acetylates histones H3 and H4 with a pattern distinct from other HAT’s. Both mouse and human BRD4 demonstrate intrinsic HAT activity. Importantly, BRD4 acetylates H3K122, a residue critical for nucleosome stability, resulting in nucleosome eviction and chromatin de-compaction. Nucleosome clearance by BRD4 occurs genome-wide, including at its targets MYC, FOS and AURKB (Aurora B kinase), resulting in increased transcription. Since BRD4 regulates transcription, these findings lead to a model where BRD4 actively links chromatin structure and transcription: It mediates chromatin de-compaction by acetylating and evicting nucleosomes of target genes, thereby activating their transcription.