title: Oncogenic Mechanisms of Histone H3 Mutations.
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.
authors.affiliation: Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York 10065.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Weinberg
authors.affiliation: Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York 10065.
authors.forename: C David
authors.initials: CD
authors.lastname: Allis
authors.affiliation: Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York 10065.
authors.forename: Chao
authors.initials: C
authors.lastname: Lu
mesh_terms: D063646:Carcinogenesis / Q000235:genetics; D002843:Chromatin / Q000235:genetics*; D005910:Glioma / Q000175:diagnosis / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006657:Histones / Q000235:genetics*; D006801:Humans; D008745:Methylation; D020125:Mutation, Missense; D011499:Protein Processing, Post-Translational
chemical_list: D002843:Chromatin; D006657:Histones; D011495:Histone-Lysine N-Methyltransferase