Hegazy Youssef A, Dhahri Hejer, El Osmani Nour, George Smitha, Chandler Darrell P, Fondufe-Mittendorf Yvonne N
Department of Epigenetics, Van Andel Research Institute, Grand Rapids, Michigan, USA.
Department of Epigenetics, Van Andel Research Institute, Grand Rapids, Michigan, USA; Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, USA.
J Biol Chem. 2025 Jan;301(1):108048. doi: 10.1016/j.jbc.2024.108048. Epub 2024 Dec 4.
Histone proteins organize nuclear DNA in eukaryotic cells and play crucial roles in regulating chromatin structure and function. Histone variants are produced by distinct histone genes and are produced independently of their canonical counterparts throughout the cell cycle. Even though histone variants may differ by only one or a few amino acids relative to their canonical counterparts, these minor variations can profoundly alter chromatin structure, accessibility, dynamics, and gene expression. Histone variants often interact with dedicated chaperones and remodelers and can have unique post-translational modifications that shape unique gene expression landscapes. Histone variants also play essential roles in DNA replication, damage repair, and histone-protamine transition during spermatogenesis. Importantly, aberrant histone variant expression and DNA mutations in histone variants are linked to various human diseases, including cancer, developmental disorders, and neurodegenerative diseases. In this review, we explore how core histone variants impact nucleosome structure and DNA accessibility, the significance of variant-specific post-translational modifications, how variant-specific chaperones and remodelers contribute to a regulatory network governing chromatin behavior, and discuss current knowledge about the association of histone variants with human diseases.
组蛋白在真核细胞中组织核DNA，并在调节染色质结构和功能方面发挥关键作用。组蛋白变体由不同的组蛋白基因产生，并且在整个细胞周期中独立于其经典对应物产生。尽管组蛋白变体相对于其经典对应物可能仅相差一个或几个氨基酸，但这些微小的变化可以深刻地改变染色质结构、可及性、动力学和基因表达。组蛋白变体通常与专门的分子伴侣和重塑因子相互作用，并可以具有独特的翻译后修饰，从而塑造独特的基因表达格局。组蛋白变体在DNA复制、损伤修复以及精子发生过程中的组蛋白-鱼精蛋白转变中也发挥着重要作用。重要的是，组蛋白变体的异常表达和DNA突变与各种人类疾病有关，包括癌症、发育障碍和神经退行性疾病。在这篇综述中，我们探讨了核心组蛋白变体如何影响核小体结构和DNA可及性、变体特异性翻译后修饰的意义、变体特异性分子伴侣和重塑因子如何促成一个控制染色质行为的调节网络，并讨论了关于组蛋白变体与人类疾病关联的当前知识。
