Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York.
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Cancer Res. 2021 Dec 15;81(24):6061-6070. doi: 10.1158/0008-5472.CAN-21-2619. Epub 2021 Sep 27.
Aberrant cell fate decisions due to transcriptional misregulation are central to malignant transformation. Histones are the major constituents of chromatin, and mutations in histone-encoding genes are increasingly recognized as drivers of oncogenic transformation. Mutations in linker histone H1 genes were recently identified as drivers of peripheral lymphoid malignancy. Loss of H1 in germinal center B cells results in widespread chromatin decompaction, redistribution of core histone modifications, and reactivation of stem cell-specific transcriptional programs. This review explores how linker histones and mutations therein regulate chromatin structure, highlighting reciprocal relationships between epigenetic circuits, and discusses the emerging role of aberrant three-dimensional chromatin architecture in malignancy.
由于转录调控失常导致的异常细胞命运决定是恶性转化的核心。组蛋白是染色质的主要成分，组蛋白编码基因的突变越来越被认为是致癌转化的驱动因素。最近发现连接组蛋白 H1 基因的突变是周围淋巴恶性肿瘤的驱动因素。生发中心 B 细胞中 H1 的缺失导致广泛的染色质解压缩、核心组蛋白修饰的重新分布以及干细胞特异性转录程序的重新激活。这篇综述探讨了连接组蛋白及其突变如何调节染色质结构，强调了表观遗传回路之间的相互关系，并讨论了异常三维染色质结构在恶性肿瘤中的新兴作用。
