Kirkiz Ecem, Meers Oliver, Grebien Florian, Buschbeck Marcus
Institute for Medical Biochemistry, University of Veterinary Medicine, Vienna, Austria.
Cancer and Leukaemia Epigenetics and Biology Program, Josep Carreras Leukaemia Research Institute (IJC), Campus Can Ruti, Badalona, Spain.
Hemasphere. 2023 Jul 11;7(8):e927. doi: 10.1097/HS9.0000000000000927. eCollection 2023 Aug.
Epigenetic regulation occurs on the level of compacting DNA into chromatin. The functional unit of chromatin is the nucleosome, which consists of DNA wrapped around a core of histone proteins. While canonical histone proteins are incorporated into chromatin through a replication-coupled process, structural variants of histones, commonly named histone variants, are deposited into chromatin in a replication-independent manner. Specific chaperones and chromatin remodelers mediate the locus-specific deposition of histone variants. Although histone variants comprise one of the least understood layers of epigenetic regulation, it has been proposed that they play an essential role in directly regulating gene expression in health and disease. Here, we review the emerging evidence suggesting that histone variants have a role at different stages of hematopoiesis, with a particular focus on the histone variants H2A, H3, and H1. Moreover, we discuss the current knowledge on how the dysregulation of histone variants can contribute to hematopoietic malignancies.
表观遗传调控发生在将DNA压缩成染色质的水平上。染色质的功能单位是核小体，它由缠绕在组蛋白核心周围的DNA组成。虽然经典组蛋白通过复制偶联过程整合到染色质中，但组蛋白的结构变体，通常称为组蛋白变体，以复制非依赖的方式沉积到染色质中。特定的伴侣蛋白和染色质重塑因子介导组蛋白变体的位点特异性沉积。尽管组蛋白变体是表观遗传调控中最不为人所了解的层面之一，但有人提出它们在健康和疾病中直接调节基因表达方面发挥着重要作用。在这里，我们综述了新出现的证据，表明组蛋白变体在造血的不同阶段发挥作用，特别关注组蛋白变体H2A、H3和H1。此外，我们讨论了目前关于组蛋白变体失调如何导致造血系统恶性肿瘤的知识。
