Dynamic Competing Histone H4 K5K8 Acetylation and Butyrylation Are Hallmarks of Highly Active Gene Promoters.
Dynamic Competing Histone H4 K5K8 Acetylation and Butyrylation Are Hallmarks of Highly Active Gene Promoters.
复制标题
DOI：
10.1016/j.molcel.2016.03.014
复制
发表时间：
2016-04-21
期刊：
影响因子：
16
通讯作者：
Khochbin S
中科院分区：
文献类型：
--
作者：
Goudarzi A;Zhang D;Huang H;Barral S;Kwon OK;Qi S;Tang Z;Buchou T;Vitte AL;He T;Cheng Z;Montellier E;Gaucher J;Curtet S;Debernardi A;Charbonnier G;Puthier D;Petosa C;Panne D;Rousseaux S;Roeder RG;Zhao Y;Khochbin S
最近发现的组蛋白赖氨酸酰化标记增加了核小体的功能多样性，远远超过乙酰化。在这里，我们集中在精子细胞分化的背景下的组蛋白丁酰化。具体地说，我们研究了组蛋白H4赖氨酸5和8在基因启动子上的丁酰化反应，其中乙酰化指导了含有溴域的蛋白质BRDT的结合，从而介导了特定阶段的基因表达程序和减数分裂后的染色质重组。全基因组作图数据显示，高活性的BRDT结合基因启动子系统地在H4-K5和H4-K8处具有竞争性的组蛋白乙酰化和丁酰化标记。尽管组蛋白丁酰化反应是转录的直接刺激物，但它与乙酰化反应竞争，特别是在H4K5处，以防止BRDT结合。此外，H4K5K8丁酰化反应也标志着后期精子发生中组蛋白去除的延缓。因此，交替的H4乙酰化和丁酰化，同时保持直接的基因激活和动态的溴域结合，可能会影响最终的男性表观基因组特征。活性基因tss以竞争H4K5K8乙酰化和丁酰化为标志，组蛋白丁酰化直接刺激转录H4K5丁酰化阻止睾丸特异基因表达的结合-驱动因素BRDT H4K5K8丁酰化与生精细胞中组蛋白的延迟去除有关，而组蛋白丁酰化促进基因转录，同时与H4K5上的乙酰化竞争以控制BRDT溴域结合。可互换H4酰化的差异染色质标记是控制基因表达和染色质重组的重要表观遗传调控机制。
Recently discovered histone lysine acylation marks increase the functional diversity of nucleosomes well beyond acetylation. Here, we focus on histone butyrylation in the context of sperm cell differentiation. Specifically, we investigate the butyrylation of histone H4 lysine 5 and 8 at gene promoters where acetylation guides the binding of Brdt, a bromodomain-containing protein, thereby mediating stage-specific gene expression programs and post-meiotic chromatin reorganization. Genome-wide mapping data show that highly active Brdt-bound gene promoters systematically harbor competing histone acetylation and butyrylation marks at H4 K5 and H4 K8. Despite acting as a direct stimulator of transcription, histone butyrylation competes with acetylation, especially at H4 K5, to prevent Brdt binding. Additionally, H4 K5K8 butyrylation also marks retarded histone removal during late spermatogenesis. Hence, alternating H4 acetylation and butyrylation, while sustaining direct gene activation and dynamic bromodomain binding, could impact the final male epigenome features. Active gene TSSs are marked by competing H4 K5K8 acetylation and butyrylation Histone butyrylation directly stimulates transcription H4K5 butyrylation prevents binding of the testis specific gene expression-driver Brdt H4K5K8 butyrylation is associated with delayed histone removal in spermatogenic cells Histone butyrylation stimulates gene transcription while competing with acetylation at H4K5 to control Brdt bromodomain binding. Differential chromatin labeling with interchangeable H4 acylations is an important epigenetic regulatory mechanism controlling gene expression and chromatin reorganization.