Assessing DNA methylation in the developing human intestinal epithelium - potential link to Inflammatory Bowel Disease

DNA methylation is one of the major epigenetic mechanisms implicated in regulating cellular development and cell type- specific gene expression. We investigated the role of DNA methylation in regulating human intestinal epithelial cell function and its potential impact on the development of inflammatory bowel diseases (IBD). Simultaneous genome-wide DNA methylation and gene expression analysis was performed on purified intestinal epithelium from human foetal and healthy paediatric gut, as well as from children newly diagnosed with IBD. Functional impact of DNA methylation on gene expression was assessed using in-vitro assays. We observed distinct differences in DNA methylation profiles between foetal and paediatric epithelium. Comparative analysis identified 214 genes for which expression is regulated via DNA methylation, i.e. regulatory differentially methylated regions (rDMRs). Pathway and functional analysis of rDMR- associated genes suggested a critical role for DNA methylation in regulating gene expression and functional development of the human intestinal epithelium. Moreover, analysis on epithelium of paediatric IBD patients revealed altered DNA methylation in genomic loci which overlap significantly with those undergoing methylation changes during intestinal development. Our study provides novel insights into the role of DNA methylation in regulating functional maturation of the human intestinal epithelium and suggest a possible link to IBD.