Ragusa Denise, Vagnarelli Paola
College of Health, Medicine and Life Sciences, Department of Life Sciences, Brunel University London, London, United Kingdom.
Front Genet. 2023 Nov 23;14:1290903. doi: 10.3389/fgene.2023.1290903. eCollection 2023.
Histone variants, which generally differ in few amino acid residues, can replace core histones (H1, H2A, H2B, and H3) to confer specific structural and functional features to regulate cellular functions. In addition to their role in DNA packaging, histones modulate key processes such as gene expression regulation and chromosome segregation, which are frequently dysregulated in cancer cells. During the years, histones variants have gained significant attention as gatekeepers of chromosome stability, raising interest in understanding how structural and functional alterations can contribute to tumourigenesis. Beside the well-established role of the histone H3 variant CENP-A in centromere specification and maintenance, a growing body of literature has described mutations, aberrant expression patterns and post-translational modifications of a variety of histone variants in several cancers, also coining the term "oncohistones." At the molecular level, mechanistic studies have been dissecting the biological mechanisms behind histones and missegregation events, with the potential to uncover novel clinically-relevant targets. In this review, we focus on the current understanding and highlight knowledge gaps of the contribution of histone variants to aneuploidy, and we have compiled a database (HistoPloidyDB) of histone gene alterations linked to aneuploidy in cancers of the The Cancer Genome Atlas project.
组蛋白变体通常在少数氨基酸残基上存在差异，它们可以取代核心组蛋白（H1、H2A、H2B和H3），赋予特定的结构和功能特征，从而调节细胞功能。除了在DNA包装中的作用外，组蛋白还调节基因表达调控和染色体分离等关键过程，而这些过程在癌细胞中经常失调。多年来，组蛋白变体作为染色体稳定性的守门人受到了广泛关注，这引发了人们对理解结构和功能改变如何导致肿瘤发生的兴趣。除了组蛋白H3变体CENP-A在着丝粒指定和维持中已确立的作用外，越来越多的文献描述了多种组蛋白变体在几种癌症中的突变、异常表达模式和翻译后修饰，还创造了“癌组蛋白”这一术语。在分子水平上，机制研究一直在剖析组蛋白和染色体错分离事件背后的生物学机制，有可能发现新的临床相关靶点。在这篇综述中，我们聚焦于目前对组蛋白变体对非整倍体贡献的理解，并突出了知识空白，我们还编制了一个与癌症基因组图谱项目中癌症非整倍体相关的组蛋白基因改变数据库（HistoPloidyDB）。
