Department of Pathology and Molecular Medicine, School of Medicine, Queen's University, Kingston, Ontario, Canada.
Department of Biology, Lomonosov Moscow State University, 1-12 Leninskie Gory, Moscow, 119991, Russia.
J Phys Chem B. 2021 Apr 29;125(16):3963-3976. doi: 10.1021/acs.jpcb.1c00694. Epub 2021 Mar 26.
At the cellular level, cancer is the disease of both the genome and the epigenome, and the interplay between genetic mutations and epigenetic states may occur at the level of elementary chromatin units, the nucleosomes. They are formed by a segment of DNA wrapped around an octamer of histone proteins. In this review, we survey various mechanisms of cancer etiology and progression mediated by histones and nucleosomes. In particular, we discuss the effects of mutations in histones, changes in their expression and slicing on epigenetic dysregulation and carcinogenesis. The links between cancer phenotypes and differential expression of histone variants and isoforms are summarized. Finally, we discourse the geometric and steric effects of DNA compaction in nucleosomes on DNA mutation rate, interactions with transcription factors, including pioneer transcription factors, and prospects of cancer cells' genome and epigenome editing.
在细胞层面上，癌症是基因组和表观基因组的疾病，遗传突变和表观状态之间的相互作用可能发生在基本染色质单位——核小体的水平上。它们由一段缠绕在组蛋白八聚体上的 DNA 组成。在这篇综述中，我们调查了由组蛋白和核小体介导的各种癌症病因和进展机制。特别是，我们讨论了组蛋白突变、其表达和切割变化对表观遗传失调和癌变的影响。总结了癌症表型与组蛋白变体和同工型差异表达之间的联系。最后，我们讨论了核小体中 DNA 压缩的几何和空间效应对 DNA 突变率、与转录因子（包括先驱转录因子）的相互作用以及癌细胞基因组和表观基因组编辑的前景。
