Synthetic Chromatin Acylation by an Artificial Catalyst System
Synthetic Chromatin Acylation by an Artificial Catalyst System
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DOI：
10.1016/j.chempr.2017.04.002
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发表时间：
2017-06-08
期刊：
影响因子：
23.5
通讯作者：
Kanai, Motomu
中科院分区：
文献类型：
--
作者：
Ishiguro, Tadashi;Amamoto, Yoshifumi;Kanai, Motomu
组蛋白乙酰化受组蛋白乙酰转移酶(HATS)和组蛋白脱乙酰基酶(HDACs)的生理调控，是基因表达的基本调控元件。最近发现了组蛋白上的新型赖氨酸酰化作用，但目前尚不清楚不同类型的组蛋白酰化作用和各种酶是如何调节染色质功能的。在这里，我们报告了一种在不依赖酶的情况下综合调节组蛋白酰化状态的方法。我们开发了一个由核小体结合催化剂和酰基供体组成的人工催化体系，它优先在组蛋白尾部乙酰化或丙二酸化赖氨酸，并抑制核小体内和核小体间的相互作用，类似于HATS。我们通过鉴定两种HDAC亚型Sirt1和SIRT6之间的位置选择性差异，以及比较组蛋白丙二酸化和乙酰化的功能，证明了我们方法的有效性。我们的体系适用于内源染色质，不需要遗传操作，因此，它可以用来剖析染色质的复杂调控。
Histone acetylation is physiologically regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) and constitutes a fundamental regulatory element in gene expression. New types of lysine acylation on histones have recently been identified, but it remains unclear how chromatin function is regulated by divergent types of histone acylation and various enzymes. Here, we report on an approach to modulating histone acylation states synthetically without relying on enzymes. We have developed an artificial catalyst system composed of nucleosome-binding catalysts and acyl donors, which preferentially acetylated or malonylated lysines on histone tails and suppressed intraand inter-nucleosome interactions similarly to HATs. We demonstrate the utility of our approach by identifying a site-selectivity difference between two HDAC isoforms, Sirt1 and Sirt6, and comparing the functions of histone malonylation and acetylation. Our system is applicable to endogenous chromatin without genetic manipulation; thus, it can be used to dissect the complex regulation of chromatin.