DNA methylation within intron 2 of the Stat1 gene is reduced in colon tissue from interleukin-10 gene-deficient mice compared with healthy control mice

Background. Epigenetic influences have been implicated in the development of autoimmunity. While such mechanisms have been linked to mouse models of intestinal inflammation, and to human inflammatory bowel disease (IBD), the involvement of epigenetic mechanisms in the pathogenesis of intestinal inflammation in the interleukin-10 gene-deficient (Il10–/–) mouse model of IBD has not yet been reported. This study investigated the hypothesis that changes observed in the expression of Stat1 and Ppara in colon tissue of Il10–/– mice are associated with differential methylation of CpG sites within key regulatory regions of these genes. Methods. Colon tissue was collected from Il10–/– and C57BL/6JArc mice at 6 (pre-inflammation) or 12 (established inflammation) weeks of age. Methylation levels of CpG sites within selected regions of the Stat1 and Ppara genes were assessed using MALDI-TOF mass spectrometry in DNA extracted from mouse colon tissue. Results. Methylation of specific CpG sites within intron 2, but not the proximal promoter, of the Stat1 gene was reduced in colon tissue from Il10–/– mice at 12 weeks of age compared with colon tissue C57BL/6J mice at 12 weeks of age. Discussion. These data provide preliminary evidence that DNA methylation is altered in the Il10–/– mouse model of IBD, and this may be linked with changes in the expression levels of genes that play a key role in inflammation. Further studies are required to confirm these observations, and to establish a causative link between methylation at specific sites (such as intron 2 of Stat1) and gene expression.