The Role of Epithelium EZH2 in Experimental Colitis

Despite recent progress, the contribution of epigenetic mechanisms to govern Inflammatory bowel disease (IBD) pathogenesis remains elusive. Here we show that epithelial EZH2, the catalytic subunit of PRC2 is critical for experimental colitis. Depletion of EZH2 in intestinal epithelial cells sensitized the cells to DSS-induced colitis in mice. To dissect underlying mechanism, we conducted gene expression profile analysis (RNA-Seq) by using primary Intestinal epithelial cells (IECs) isolated from EZH2 WT and KO mice to gain molecular insights into the affected biological processes. To this end, colorectal epithelial cells were isolated after 3 days of 2% DSS treatment, in which day EZH2-depleted mice did not display the obviously morphological defects in comparison with control littermates. IECs were isolated by EDTA isolation buffer. Each sample contains pooled prostate RNA from 5 mice, and was subjected to Hiseq RNA-Seq, performed by BGI Tech Solutions Co., Ltd. There was total 1018 genes up-regulated after EZH2 depletion, respectively. Gene ontology (GO) analysis revealed that the most prominent biological processes altered were associated with immune and inflammatory response. Likewise, unbiased Ingenuity Pathway Analysis (IPA) indicated that TNF-alpha and INF-gamma serve as the top upstream regulators to modulate gene changes in EZH2-depleted cells. In addition, a sub-set of apoptotic were altered after EZH2 depletion. Overall design: Genome-wide expression profiling of primary colon epethelial cells isolated form EZH2 WT and EZH2-IEC-KO mice which are treated with 2% DSS for 3 days.Each is tested in duplicate.