Inflammatory bowel disease (IBD) is an important risk factor for colorectal cancer (CRC) development. Several studies have detected disordered methylation patterns induced by inflammatory bowel disease in mouse model, suggesting that epigenetic dysregulation may provide a key mechanistic link between IBD and CRC. In the present study, we employed a multi-omics approach to characterize epigenetic changes associated with IBD in an established model of human IBD: IL10-/- Rag2-/- mice infected with Helicobacter hepaticus. In addition to DNA methylation, we have focused on novel DNA epigenetic mark, 5-hydroxymethylcytosine (5hmC), which is generated from 5-methylcytosine (5mC) via Ten-eleven-translocation enzyme (TET) mediated oxidation. First of all, we mapped DNA methylome and hydroxymethylome in mouse proximal colon via reduced representative bisulfite sequencing (RRBS) combined with oxidized RRBS (Ox-RRBS). In addition, we employed RNA-seq to characterize the changes in gene expression patterns in same tissue. Our results showed that the inflammation in mouse proximal colon is accompanied by a global decrease of DNA hydroxymethylation. Interestingly, differentially methylated region(DMR) and differentially hydroxymethylated region(DhMR) are enriched in genes that are correlated with gastrointestinal disease, inflammatory disease and cancer. Furthermore, the corresponding transcriptome showed an initial feature of colorectal cancer. Taken together, our results suggest a potential epigenetic mechanism for the initiation of inflammation mediated colorectal cancer.

Multi-omics characterization of an inflammatory bowel disease mouse model

2019 Fall National Meeting

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