Inflammatory bowel disease (IBD) with its two main manifestations Crohn’s disease (CD) and ulcerative colitis (UC) are chronic gastrointestinal disorders with unknown aetiology and no cure (Kaser, 2010). Immunochip experiments have identified about 200 IBD risk loci across the genome (Jostins, 2012, Liu, 2015), which however could only partially explain why IBD has such high heritability, a discrepancy known as ‘missing heritability’ (Zuk, 2012). IBD has dramatically risen in incidence over the last decades in the Western world, and more recently in countries adopting Western lifestyles (Loftus, 2004). Concordance rates in monozygotic twins of 40-50% and 10-15% in CD and UC, respectively, indicate the relative contribution of genetic vs environmental risks (Moller, 2015). This suggests that other than genetic factors might be inherited in IBD pointing at epigenetic alterations (change of DNA methylation). Indeed, intestinal tissues of IBD patients display aberrant DNA methylation profiles compared to healthy individuals (Lin, 2012; Häsler, 2012; Cooke, 2012).
To investigate a potential disease-contributing role of DNA methylation alterations in IBD we will establish a trans-generational in vivo model mimicking this scenario. Moreover, we will generate cell-type-specific and genome-wide maps of the inflammation-methylome and –transcriptome of different intestinal cell subsets as well as of sperm samples of mice of the F0 and F1 generation (inflamed vs. healthy) by subjecting them to next-generation transcriptome (RNA-seq) and methylome (Representation Bisulfite Sequencing –RRBS) sequencing.