A Subset of Human Bromodomains Recognizes Butyryllysine and Crotonyllysine Histone Peptide Modifications
A Subset of Human Bromodomains Recognizes Butyryllysine and Crotonyllysine Histone Peptide Modifications
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DOI：
10.1016/j.str.2015.08.004
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发表时间：
2015-10-06
期刊：
影响因子：
5.7
通讯作者：
Cochran, Andrea G.
中科院分区：
文献类型：
--
作者：
Flynn, E. Megan;Huang, Oscar W.;Cochran, Andrea G.
溴域是表观遗传阅读器，被招募到组蛋白尾部的乙酰赖氨酸残基上。最近的研究已经确定了非乙酰酰基赖氨酸的修饰，增加了这些修饰可能被溴域读取的可能性。对几乎完整的人溴结构域家族的分析表明，虽然大多数人的溴结构域只结合较短的乙酰和丙酰标记，但BRD9、CECR2和TAF1的第二个溴结构域也识别较长的丁酰标记。此外，TAF1第二溴结构域能够结合巴豆基标记。所有被测试的人溴域都不能结合琥珀酰基标记。我们从结构和生化上表征了与不同酰基的结合，鉴定了溴域残基和有助于特异性的结构属性。这些研究表明，在某些人类溴域中具有惊人的可塑性，但没有单一因素控制整个家族的特异性。对候选丁酰基和巴豆酰赖氨酸阅读器的鉴定支持了这些标记可能具有特定生理功能的观点。
Bromodomains are epigenetic readers that are recruited to acetyllysine residues in histone tails. Recent studies have identified non- acetyl acyllysine modifications, raising the possibility that these might be read by bromodomains. Profiling the nearly complete human bromodomain family revealed that while most human bromodomains bind only the shorter acetyl and propionyl marks, the bromodomains of BRD9, CECR2, and the second bromodomain of TAF1 also recognize the longer butyryl mark. In addition, the TAF1 second bromodomain is capable of binding crotonyl marks. None of the human bromodomains tested binds succinyl marks. We characterized structurally and biochemically the binding to different acyl groups, identifying bromodomain residues and structural attributes that contribute to specificity. These studies demonstrate a surprising degree of plasticity in some human bromodomains but no single factor controlling specificity across the family. The identification of candidate butyryl- and crotonyllysine readers supports the idea that these marks could have specific physiological functions.