Examples of post-translational modulation of Polycomb group and associated proteins. (a) Simplified model of Polycomb Group (PcG)-mediated repression. The histone methyltransferase EZH2 trimethylates histone H3 at lysine 27, this mark is recognized by chromobox homolog (CBX) proteins via the chromodomain. RNF2/RING1 homologs are E3 ubiquitin ligases for H2A; RYBP binds H2AK119Ub1. Combined, these activities induce/maintain transcriptional repression. Gray boxes depict Polycomb Repressive Complex (PRC)-associated, epigenetically relevant enzymatic activities. (b) RNF2 E3 ligase activity is significantly enhanced in the presence of BMI1 or phosphorylated PCGF2. (c) DNA damage-induced phosphorylation of HIPK2 leads to phosphorylation of CBX4. Phosphorylation of CBX4 at T495 in turn enhances the HIPK2 sumoylation. (d) AKT-induced phosphorylation of EZH2 on S21 impairs its binding to histone H3, thereby inhibiting H3K27 trimethylation. me = methylation, ph = phosphorylation, su = sumoylation; ub = ubiquitylation.