State Key Laboratory of Natural and Biomimetic Drugs, Chemical Biology Center, Department of Molecular and Cellular, Pharmacology, Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
Center for Synthetic Biochemistry, Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
Angew Chem Int Ed Engl. 2022 Jul 25;61(30):e202205570. doi: 10.1002/anie.202205570. Epub 2022 Jun 14.
Structurally diverse acylations have been identified as post-translational modifications (PTMs) on histone lysine residues, but their functions and regulations remain largely unknown. Interestingly, in nature, a lysine acylation analog, pyrrolysine, is introduced as a co-translational modification (CTM) through genetic encoding. To explore this alternative life form, we created a model organism Saccharomyces cerevisiae containing site-specific lysine CTMs (acetyl-lysine, crotonyl-lysine, or another synthetic analog) at histone H3K56 using non-canonical amino acid mutagenesis to afford a chemically modified nucleosome in lieu of their own in vivo. We further demonstrated that acetylation of histone H3K56 partly tends to provide a more favorable chromatin environment for DNA repair in yeast compared to crotonylation and crosstalk with other PTMs differently. This study provides a potentially universal approach to decipher the consequences of different histone lysine PTMs in eukaryotes.
结构多样的酰化被鉴定为组蛋白赖氨酸残基上的翻译后修饰（PTM），但其功能和调控仍知之甚少。有趣的是，在自然界中，赖氨酸酰化类似物吡咯赖氨酸通过遗传编码被引入为共翻译修饰（CTM）。为了探索这种替代的生命形式，我们使用非天然氨基酸诱变在酿酒酵母中创建了一个含有组蛋白 H3K56 位特异性赖氨酸 CTM（乙酰-赖氨酸、巴豆酰-赖氨酸或其他合成类似物）的模式生物，从而在体内用化学修饰的核小体代替其自身。我们进一步证明，与巴豆酰化和与其他 PTM 的不同串扰相比，组蛋白 H3K56 的乙酰化部分倾向于为酵母中的 DNA 修复提供更有利的染色质环境。这项研究为破译真核生物中不同组蛋白赖氨酸 PTM 的后果提供了一种潜在的通用方法。
