Fig. 4

Effects of metabolites on post-translational modification of EZH2 protein. Post-translational modification of EZH2 requires metabolites to participate. EZH2 acetylation by P300/CBP-related factor (PCAF) uses the metabolite acetyl-CoA, enhancing the stability of EZH2. Acetyl-CoA is synthesized in the cytoplasm and nucleus from acetate, citrate, or pyruvate by acyl-CoA synthetase short-chain family member 2 (ACSS2), ATP-citrate lyase (ACLY), and pyruvate dehydrogenase complex (PDC), respectively. EZH2 GlcNAcylation is mediated by O-GlcNAc transferase (OGT) utilizing UDP-glucosamine (UDP-GlcNAc) which is generated from the hexosamine biosynthetic pathway. The stability and function of EZH2 is enhanced by O-GlcNAcylation modification. Energetic stress can affect EZH2 phosphorylation by activating AMP-activated protein kinase (AMPK), leading to a decrease in PRC2 stability and EZH2 activity