Department of Chemistry, University of Hong Kong, Pokfulam Road, Hong Kong, China.
School of Biological Sciences, University of Hong Kong, Pokfulam Road, Hong Kong, China.
Mol Cell. 2019 Nov 21;76(4):660-675.e9. doi: 10.1016/j.molcel.2019.08.018. Epub 2019 Sep 18.
Histone posttranslational modifications (PTMs) regulate chromatin structure and dynamics during various DNA-associated processes. Here, we report that lysine glutarylation (Kglu) occurs at 27 lysine residues on human core histones. Using semi-synthetic glutarylated histones, we show that an evolutionarily conserved Kglu at histone H4K91 destabilizes nucleosome in vitro. In Saccharomyces cerevisiae, the replacement of H4K91 by glutamate that mimics Kglu influences chromatin structure and thereby results in a global upregulation of transcription and defects in cell-cycle progression, DNA damage repair, and telomere silencing. In mammalian cells, H4K91glu is mainly enriched at promoter regions of highly expressed genes. A downregulation of H4K91glu is tightly associated with chromatin condensation during mitosis and in response to DNA damage. The cellular dynamics of H4K91glu is controlled by Sirt7 as a deglutarylase and KAT2A as a glutaryltransferase. This study designates a new histone mark (Kglu) as a new regulatory mechanism for chromatin dynamics.
组蛋白翻译后修饰（PTMs）在各种与 DNA 相关的过程中调节染色质结构和动态。在这里，我们报告说赖氨酸戊二酰化（Kglu）发生在人类核心组蛋白的 27 个赖氨酸残基上。使用半合成戊二酰化组蛋白，我们表明在体外，进化上保守的组蛋白 H4K91 上的 Kglu 使核小体不稳定。在酿酒酵母中，通过模拟 Kglu 的谷氨酸取代 H4K91 会影响染色质结构，从而导致转录全局上调以及细胞周期进程、DNA 损伤修复和端粒沉默缺陷。在哺乳动物细胞中，H4K91glu 主要富集在高表达基因的启动子区域。H4K91glu 的下调与有丝分裂期间的染色质浓缩以及对 DNA 损伤的反应密切相关。H4K91glu 的细胞动力学由去戊二酰基酶 Sirt7 和戊二酰基转移酶 KAT2A 控制。这项研究将一种新的组蛋白标记（Kglu）指定为染色质动力学的新调节机制。
