Epigenetic alterations, especially histone modification, play vital roles in the pathogenesis of colon cancer. Upregulation of the enhancer of zeste homolog 2 (EZH2) has been reported to contribute to the initiation and progression of colon cancer. This study analyzed the association between EZH2 and phosphorylation of H2B at tyrosine 37 (H2B^Y37ph ) in colon cancer tissues and cells, along with the influences of the EZH2-H2B^Y37ph axis on colon cancer cell autophagy. Immunohistochemistry was utilized to assess EZH2 and H2B^Y37ph expressions in clinical samples of colon cancer. Cell transfection was carried out to alter EZH2 and H2B^Y37ph expressions in colon cancer cells. Co-immunoprecipitation analysis and glutathione-S-transferase (GST) pull down assay were conducted to analyze the association between EZH2 and H2B^Y37ph . Western blotting was utilized to measure proteins expressions related to cell autophagy. We found that there was a positive association between EZH2 and H2B^Y37ph in colon cancer tissues and cells. EZH2 directly interacted with H2B and promoted H2B^Y37ph in colon cancer cells using ATP as a phosphate donor. Moreover, EZH2 levated colon cancer cell autophagy in starvation condition. H2B^Y37ph was required for EZH2-elevated colon cancer cell autophagy under starvation condition. The EZH2-H2B^Y37ph axis elevated colon cancer cell autophagy possibly via activating transcriptional regulation of ATG genes. In conclusion, EZH2-elevated colon cancer initiation and progression at least in part via inducing colon cancer cell autophagy. EZH2 could phosphorylate H2B^Y37 and then induce transcription activation of ATG genes in colon cancer cells under starvation condition.

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