Abstract
Oncohistones have emerged as a new area in cancer epigenetics research. Recent efforts to catalogue histone mutations in cancer patients have revealed thousands of histone mutations across different types of cancer. In contrast to previously identified oncohistones (H3K27M, H3G34V/R, and H3K36M), where the mutations occur on the tail domain and affect histone post-translational modifications, the majority of the newly identified mutations are located within the histone fold domain and affect gene expression via distinct mechanisms. The recent characterization of the selected H2B has revealed previously unappreciated roles of oncohistones in nucleosome stability, chromatin accessibility, and chromatin remodeling. This review summarizes recent advances in the study of H2B oncohistones and other emerging oncohistones occurring on other types of histones, particularly those occurring on the histone fold domain.
Highlights
The nucleosome is the basic repeating unit of the chromatin
Oncohistones have been an active area of research since 2010, starting with the identification of H3K27M (Histone H3 Lys27-to-Met missense mutation) and H3G34V/R in diffuse intrinsic pontine gliomas [4,5,6], closely followed by the report of H3K36M in chondroblastomas [7] and head and neck squamous cell carcinomas [8,9]
Oncohistones referred exclusively to H3 mutants, namely H3K27M, H3G34V/R, and H3K36M. These classical oncohistones are restricted to several types of cancers and promote tumorigenesis mainly through the perturbation of gene transcription via alterations in histone modifications
Summary
The nucleosome is the basic repeating unit of the chromatin. Each nucleosome consists of two copies each of H2A, H2B, H3, and H4. Oncohistones have been an active area of research since 2010, starting with the identification of H3K27M (Histone H3 Lys27-to-Met missense mutation) and H3G34V/R in diffuse intrinsic pontine gliomas [4,5,6], closely followed by the report of H3K36M in chondroblastomas [7] and head and neck squamous cell carcinomas [8,9] These mutations are found in diverse cancer types, they converge functionally to perturb histone post-translational modification and lead to aberrant gene expression. Some of the most prevalent mutations occur in the globular histone fold domain and are situated in regions important for the structural integrity of the nucleosome, leading to speculation that oncohistones might impede cellular processes beyond histone modifications. This review summarizes recent studies on histone fold mutants occurring in H2B including H2BG53D, H2BE76K/Q, and H2BE113K mutations
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