Title | Oncogenic Mechanisms of Histone H3 Mutations. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Weinberg DN, C Allis D, Lu C |
Journal | Cold Spring Harb Perspect Med |
Volume | 7 |
Issue | 1 |
Date Published | 2017 Jan 03 |
ISSN | 2157-1422 |
Keywords | Carcinogenesis, Chromatin, Glioma, Histone-Lysine N-Methyltransferase, Histones, Humans, Methylation, Mutation, Missense, Protein Processing, Post-Translational |
Abstract | Recurrent missense mutations in histone H3 were recently reported in pediatric gliomas and soft tissue tumors. Strikingly, these mutations only affected a minority of the total cellular H3 proteins and occurred at or near lysine residues at positions 27 and 36 on the amino-terminal tail of H3 that are subject to well-characterized posttranslational modifications. Here we review recent progress in elucidating the mechanisms by which these mutations perturb the chromatin landscape in cells through their effects on chromatin-modifying machinery, particularly through inhibition of specific histone lysine methyltransferases. One common feature of histone mutations is their ability to arrest cells in a primitive state refractory to differentiation induction, highlighting the importance of studying these mutations in their proper developmental context. |
DOI | 10.1101/cshperspect.a026443 |
Alternate Journal | Cold Spring Harb Perspect Med |
PubMed ID | 27864305 |
PubMed Central ID | PMC5204328 |
Grant List | K99 CA212257 / CA / NCI NIH HHS / United States P01 CA196539 / CA / NCI NIH HHS / United States T32 CA009673 / CA / NCI NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States |
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