Simpson Querrey Institute for Epigenetics and the Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Sci Adv. 2023 Apr 21;9(16):eadg6593. doi: 10.1126/sciadv.adg6593.
The past three decades have yielded a wealth of information regarding the chromatin regulatory mechanisms that control transcription. The "histone code" hypothesis-which posits that distinct combinations of posttranslational histone modifications are "read" by downstream effector proteins to regulate gene expression-has guided chromatin research to uncover fundamental mechanisms relevant to many aspects of biology. However, recent molecular and genetic studies revealed that the function of many histone-modifying enzymes extends independently and beyond their catalytic activities. In this review, we highlight original and recent advances in the understanding of noncatalytic functions of histone modifiers. Many of the histone modifications deposited by these enzymes-previously considered to be required for transcriptional activation-have been demonstrated to be dispensable for gene expression in living organisms. This perspective aims to prompt further examination of these enigmatic chromatin modifications by inspiring studies to define the noncatalytic "epigenetic moonlighting" functions of chromatin-modifying enzymes.
过去三十年产生了大量关于控制转录的染色质调控机制的信息。“组蛋白密码”假说——假设不同组合的翻译后组蛋白修饰被下游效应蛋白“读取”以调节基因表达——指导染色质研究揭示了与生物学许多方面相关的基本机制。然而，最近的分子和遗传研究表明，许多组蛋白修饰酶的功能独立于其催化活性而延伸。在这篇综述中，我们强调了对组蛋白修饰酶非催化功能的理解的最新进展。这些酶沉积的许多组蛋白修饰——以前被认为是转录激活所必需的——已经被证明在活体生物中对基因表达不是必需的。这一观点旨在通过激发研究来定义染色质修饰酶的非催化“表观遗传兼职”功能，从而进一步研究这些神秘的染色质修饰。
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