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.