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化学催化剂介导的活细胞合成组蛋白乙酰化

Live Cell Synthetic Histone Acetylation by Chemical Catalyst.

作者信息

Kawashima Shigehiro A, Kanai Motomu

机构信息

Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.

出版信息

Methods Mol Biol. 2023;2519:155-161. doi: 10.1007/978-1-0716-2433-3_17.

Abstract

Posttranslational modifications (PTMs) of histones, such as lysine acetylation and ubiquitination, regulate chromatin structure and gene expression. In living organisms, histone PTMs are catalyzed by histone-modifying enzymes. Here, we describe an entirely chemical method to introduce histone modifications in living cells without genetic manipulation. The chemical catalyst PEG-LANA-DSSMe activates a thioester acetyl donor, N,S-diacetylcysteamine (NAC-Ac), and promotes regioselective, synthetic histone acetylation at H2BK120 in living cells.

摘要

组蛋白的翻译后修饰(PTM),如赖氨酸乙酰化和泛素化,可调节染色质结构和基因表达。在活生物体中,组蛋白PTM由组蛋白修饰酶催化。在此,我们描述了一种无需基因操作即可在活细胞中引入组蛋白修饰的完全化学方法。化学催化剂聚乙二醇-兰尼碱-二硫代琥珀酰亚胺甲基酯(PEG-LANA-DSSMe)激活硫酯乙酰供体N,S-二乙酰半胱胺(NAC-Ac),并促进活细胞中H2BK120位点的区域选择性合成组蛋白乙酰化。

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