Genome-wide Profiling of H3K27ac binding in human cancer cell lines

Upregulation of enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and its associated histone H3 lysine 27 (H3K27) trimethylation frequently occur in human cancer, yet both preclinical and clinical evidence suggested the very limited benefit of EZH2-targeted therapies. This study investigated the underlying mechanisms from a perspective of EZH2 inhibition-caused histone modification crosstalk. A mass spectrometry approach enabled us discovering the alteration of global histone modifications responding to EZH2 inhibition. Feedback upregulation of H3K27 acetylation (H3K27ac) level is closely associated with limited drug response to EZH2 inhibition across multiple cancer types. H3K27ac alteration caused transcriptional activation of oncoproteins confers drug resistant to EZH2 inhibition. Here we used ChIP-Seq analysis to identify the alteration of genome-wide H3K27ac bingding sites with EZH2 inhibitor treatment in human cancer cell lines. Examination of H3K27ac modification in 3 human cancer cell lines （Pfeiffer, U2932 and SMMC-7721）.