Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Mol Cell. 2022 Aug 18;82(16):2925-2938. doi: 10.1016/j.molcel.2022.07.008.
Work over the last decade has uncovered a new layer of epigenetic dysregulation. It is now appreciated that somatic missense mutations in histones, the packaging agents of genomic DNA, are often associated with human pathologies, especially cancer. Although some of these "oncohistone" mutations are thought to be key drivers of cancer, the impacts of the majority of them on disease onset and progression remain to be elucidated. Here, we survey this rapidly expanding research field with particular emphasis on how histone mutants, even at low dosage, can corrupt chromatin states. This work is unveiling the remarkable intricacies of epigenetic control mechanisms. Throughout, we highlight how studies of oncohistones have leveraged, and in some cases fueled, the advances in our ability to manipulate and interrogate chromatin at the molecular level.
在过去的十年中，研究揭示了表观遗传调控失常的一个新层面。现在人们已经认识到，组蛋白（基因组 DNA 的包装剂）中的体细胞错义突变常常与人类疾病相关，尤其是癌症。虽然这些“癌组蛋白”突变中的一些被认为是癌症的关键驱动因素，但它们中大多数对疾病的发生和进展的影响仍有待阐明。在这里，我们特别强调了即使在低剂量下，组蛋白突变体如何破坏染色质状态，来调查这个快速发展的研究领域。这项工作揭示了表观遗传调控机制的惊人复杂性。在整个过程中，我们强调了癌组蛋白研究如何利用，并且在某些情况下推动了我们在分子水平上操纵和探究染色质的能力的提高。
