核小体构成染色质的基本组成部分。它们由包裹在组蛋白八聚体周围的 DNA 组成，该八聚体由四个核心组蛋白 H2A、H2B、H3 和 H4 各两个副本组成。核小体组蛋白经历大量翻译后修饰，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模板过程。鉴于它们的对称排列，核小体内的姐妹组蛋白通常被认为是等效的并且携带相同的修饰。然而，现在很清楚，核小体可以表现出不对称性，在单个核小体内结合差异修饰的姐妹组蛋白或同一组蛋白的不同变体。通过开发允许生成不对称修饰核小体的新工具，最近的生化和细胞研究已开始揭示核小体不对称的起源和功能后果。这些研究表明，核小体不对称代表了染色质状态建立和功能读出的一种新的调节机制。不对称性扩大了可用于在单个核小体上设置复杂组蛋白标记的组合空间，调节与组蛋白修饰剂和读者的多价相互作用。不对称性所产生的功能后果调节转录、二价染色质发育基因表达的平衡，以及癌组蛋白解除癌症中染色质状态的调节机制。在这里，我们回顾了揭示核小体不对称机制和生物学功能的最新进展和当前挑战。© 2024 作者。

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.© 2024 The Author(s).