Nucleosomal asymmetry: a novel mechanism to regulate nucleosome function.

IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical Society transactions Pub Date : 2024-06-26 DOI:10.1042/BST20230877
Devisree Valsakumar, Philipp Voigt
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Abstract

Nucleosomes constitute the fundamental building blocks of chromatin. They are comprised of DNA wrapped around a histone octamer formed of two copies each of the four core histones H2A, H2B, H3, and H4. Nucleosomal histones undergo a plethora of posttranslational modifications that regulate gene expression and other chromatin-templated processes by altering chromatin structure or by recruiting effector proteins. Given their symmetric arrangement, the sister histones within a nucleosome have commonly been considered to be equivalent and to carry the same modifications. However, it is now clear that nucleosomes can exhibit asymmetry, combining differentially modified sister histones or different variants of the same histone within a single nucleosome. Enabled by the development of novel tools that allow generating asymmetrically modified nucleosomes, recent biochemical and cell-based studies have begun to shed light on the origins and functional consequences of nucleosomal asymmetry. These studies indicate that nucleosomal asymmetry represents a novel regulatory mechanism in the establishment and functional readout of chromatin states. Asymmetry expands the combinatorial space available for setting up complex sets of histone marks at individual nucleosomes, regulating multivalent interactions with histone modifiers and readers. The resulting functional consequences of asymmetry regulate transcription, poising of developmental gene expression by bivalent chromatin, and the mechanisms by which oncohistones deregulate chromatin states in cancer. Here, we review recent progress and current challenges in uncovering the mechanisms and biological functions of nucleosomal asymmetry.

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核小体不对称:调节核小体功能的新机制
核小体是染色质的基本组成部分。核小体由 DNA 组成,外面包着组蛋白八聚体,组蛋白八聚体由四种核心组蛋白 H2A、H2B、H3 和 H4 各两份组成。核糖体组蛋白经过大量的翻译后修饰,通过改变染色质结构或招募效应蛋白来调节基因表达和其他染色质引发的过程。鉴于核小体的对称排列,核小体内的姐妹组蛋白通常被认为是等同的,并携带相同的修饰。然而,现在已经很清楚,核小体可以表现出不对称性,在单个核小体内结合了不同修饰的姐妹组蛋白或同一组蛋白的不同变体。由于开发出了可生成不对称修饰核小体的新型工具,最近的生化研究和基于细胞的研究已开始揭示核小体不对称的起源和功能性后果。这些研究表明,核小体不对称是染色质状态建立和功能读出的一种新型调控机制。不对称性扩大了可用于在单个核小体上建立复杂组蛋白标记集的组合空间,调节了与组蛋白修饰物和阅读器的多价相互作用。由此产生的不对称功能性后果可调节转录、二价染色质对发育基因表达的调控,以及共价组蛋白对癌症染色质状态的失调机制。在此,我们回顾了在揭示核小体不对称的机制和生物学功能方面的最新进展和当前挑战。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biochemical Society transactions
Biochemical Society transactions 生物-生化与分子生物学
CiteScore
7.80
自引率
0.00%
发文量
351
审稿时长
3-6 weeks
期刊介绍: Biochemical Society Transactions is the reviews journal of the Biochemical Society. Publishing concise reviews written by experts in the field, providing a timely snapshot of the latest developments across all areas of the molecular and cellular biosciences. Elevating our authors’ ideas and expertise, each review includes a perspectives section where authors offer comment on the latest advances, a glimpse of future challenges and highlighting the importance of associated research areas in far broader contexts.
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