Figure 1.

(A) In DIPG, there is global hypomethylation of Lys27 of H3, which promotes a more accessible chromatin state characterized by H3K27 acetylation and aberrant gene expression. Histone H3.1 or H3.3 harbors a K27M aberration. The mutant K27 histone inhibits PRC2, which is the major H3K27 methylase. (B) Treatment of DIPG with an epigenetic modifier – in the cartoon GSKJ4 – restores methylation at H3K27 toward the physiological state, causing tumor shrinkage. Reprinted by permission from Macmillan Publishers Ltd: Nature Genetics [May; 46(5):457–61], copyright 2014.