Histone H1 Mutations in Lymphoma: A Link(er) between Chromatin Organization, Developmental Reprogramming, and Cancer.

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. ©2021 American Association for Cancer Research.