Histones serve to both package and organize DNA within the nucleus. In addition to histone post-translational modification and chromatin remodelling complexes, histone variants contribute to the complexity of epigenetic regulation of the genome. Histone variants are characterized by a distinct protein sequence and a selection of designated chaperone systems and chromatin remodelling complexes that regulate their localization in the genome. In addition, histone variants can be enriched with specific post-translational modifications, which in turn can provide a scaffold for recruitment of variant-specific interacting proteins to chromatin. Thus, through these properties, histone variants have the capacity to endow specific regions of chromatin with unique character and function in a regulated manner. In this Review, we provide an overview of recent advances in our understanding of the contribution of histone variants to chromatin function in mammalian systems. First, we discuss new molecular insights into chaperone-mediated histone variant deposition. Next, we discuss mechanisms by which histone variants influence chromatin properties such as nucleosome stability and the local chromatin environment both through histone variant sequence-specific effects and through their role in recruiting different chromatin-associated complexes. Finally, we focus on histone variant function in the context of both embryonic development and human disease, specifically developmental syndromes and cancer.

组蛋白在细胞核内包装和组织 DNA。除了组蛋白翻译后修饰和染色质重塑复合物之外，组蛋白变异还导致基因组表观遗传调控的复杂性。组蛋白变体的特征在于独特的蛋白质序列以及一系列指定的伴侣系统和染色质重塑复合物，这些复合物调节它们在基因组中的定位。此外，组蛋白变体可以通过特定的翻译后修饰来富集，这反过来又可以为将变体特异性相互作用蛋白招募到染色质提供支架。因此，通过这些特性，组蛋白变体能够以受调控的方式赋予染色质特定区域独特的特征和功能。在这篇综述中，我们概述了我们对哺乳动物系统中组蛋白变异对染色质功能的贡献的理解的最新进展。首先，我们讨论分子伴侣介导的组蛋白变异体沉积的新分子见解。接下来，我们讨论组蛋白变体通过组蛋白变体序列特异性效应及其在招募不同染色质相关复合物中的作用来影响染色质特性（例如核小体稳定性和局部染色质环境）的机制。最后，我们关注胚胎发育和人类疾病（特别是发育综合征和癌症）背景下的组蛋白变异功能。