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.

过去十年的工作揭示了新的表观遗传失调。现在人们认识到，组蛋白（基因组 DNA 的包装剂）中的体细胞错义突变通常与人类病理，尤其是癌症有关。尽管其中一些“癌组蛋白”突变被认为是癌症的关键驱动因素，但其中大多数突变对疾病发生和进展的影响仍有待阐明。在这里，我们调查了这个快速扩展的研究领域，特别强调组蛋白突变体即使在低剂量下也如何破坏染色质状态。这项工作揭示了表观遗传控制机制的显着复杂性。在整个过程中，我们强调了癌组蛋白的研究如何利用并在某些情况下推动了我们在分子水平上操纵和询问染色质的能力的进步。