PRC2 and regulation of histone H3 K27 methylation levels. PRC2 catalyzes K27 di- and trimethylation of histone H3. PRC2 consists of 4 main protein components: EZH2, SUZ12, EED, and RBBP4, as well as additional accessory proteins ASXL1, AEBP2, JARID2, and the polycomblike proteins. Normal catalytic functions are shown on the right side of the figure: methylated H3 K27 is recognized by PRC1, which catalyzes the ubiquitination of K119 on histone H2A, which in turn attracts the DNA methyltransferases to confer a repressive chromatin conformation to the region. Two enzymes demethylate the K27 position, KDM6A/UTX and KDM6B/JMJD3. In contrast, H3 K27^M/I mutations, shown on the left side of the figure, prevent PRC2 from catalyzing methylation at this residue of the histone tail. These mutations show cooperativity with RUNX1 mutations in driving leukemia development.¹  DNMTS, DNA methyltransferases; me, methylation; mut, mutation; PCLS, polycomb-like proteins; ub, ubiquitination. Professional illustration by Somersault18:24.