Molecular Coupling of Histone Crotonylation and Active Transcription by AF9 YEATS Domain.
Molecular Coupling of Histone Crotonylation and Active Transcription by AF9 YEATS Domain.
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AF9 YEATS 结构域对组蛋白巴豆酰化和主动转录的分子偶联。
DOI：
10.1016/j.molcel.2016.03.028
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发表时间：
2016-04-21
期刊：
影响因子：
16
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Li Y;Sabari BR;Panchenko T;Wen H;Zhao D;Guan H;Wan L;Huang H;Tang Z;Zhao Y;Roeder RG;Shi X;Allis CD;Li H
染色质结合蛋白模块（“阅读器”）对组蛋白共价修饰的识别构成了表观遗传调控的主要机制，典型的是结合乙酰赖氨酸的溴结构域。非乙酰化组蛋白赖氨酸酰化（如巴豆酰化，丁基酰化，丙酸酰化等）最近已被确定，但读者更喜欢这些酰化尚未表征。在这里，我们报道了AF9 YEATS结构域对乙酰赖氨酸的crotonyl-表现出选择性的高结合亲和力。结构研究揭示了一个扩展的芳香族夹笼，该夹笼是由芳香族环与芳香族环之间的π-芳香族和疏水相互作用引起的。这些特征在叶芝中是保守的，但在溴域中不是。利用基于细胞的模型，我们发现AF9与crotonylated组蛋白H3共定位，并以YEATS结构域依赖的方式正向调节基因表达。我们的研究将进化上保守的YEATS结构域定义为一个crotonylysine读取器家族，并特别证明了AF9的YEATS结构域直接将组蛋白crotonylation与活性转录联系起来。
Recognition of histone covalent modifications by chromatin-binding protein modules (“readers”) constitutes a major mechanism for epigenetic regulation, typified by bromodomains that bind acetyllysine. Non-acetyl histone lysine acylations (e.g. crotonylation, butyrylation, propionylation etc.) have been recently identified, however readers that prefer these acylations have not been characterized. Here we report that the AF9 YEATS domain displays selectively higher binding affinity for crotonyl- over acetyl-lysine. Structural studies revealed an extended aromatic sandwiching cage with crotonyl-specificity arising from π-aromatic and hydrophobic interactions between crotonyl and aromatic rings. These features are conserved among the YEATS, but not the bromodomains. Utilizing a cell-based model, we showed that AF9 co-localizes with crotonylated histone H3 and positively regulates gene expression in a YEATS domain-dependent manner. Our studies define the evolutionarily conserved YEATS domain as a family of crotonyllysine readers and specifically demonstrate that the YEATS domain of AF9 directly links histone crotonylation to active transcription.