[PERSPECTIVES] Oncogenic Mechanisms of Histone H3 Mutations

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.

Source: Cold Spring Harbor perspectives in medicine - January 2, 2017 Category: Research Authors: Weinberg, D. N., Allis, C. D., Lu, C. Tags: Chromatin Deregulation in Cancer PERSPECTIVES Source Type: research