Fig. 7: Conditional deletion of Dnmt3a in IECs increases susceptibility to inflammation.

Chronic colitis was induced by cyclic administration of 2% DSS (n = 6 female animals/group). Weight loss (a) and diseases activity index (DAI) score (b) were monitored every other day until day 30. c Colon mRNA expression levels of proliferative markers Olfm4 and Ccnd1 in crypts isolated from Dnmt3a^ΔIEC and Dnmt3a^fl/fl mice (qRT-PCR) in chronic DSS colitis at day 30 of the experiment. Murine beta-actin was used as housekeeping gene (n = 6). d Acute inflammation experimental model workflow (early inflammation group (day 5) n = 5, recovery post-DSS group (day 12) n = 8). Graphical elements modified from ref. 74. e Fecal blood content on day 5 (n = 6/7). f Representative images and quantification of BrdU-positive cells from colonic sections of Dnmt3a^ΔIEC and Dnmt3a^fl/fl mice. A minimum of 100 crypts/section were assessed. Each dot represents each animal (n = 3/5 day 5, n = 6 day 12). g Gene ontology (GO) analysis for processes enriched in differentially methylated promoters 5 and 12 days after DSS treatment in Dnmt3a^ΔIEC and Dnmt3a^fl/fl mice. Dot size is proportional to the statistical significance of the enrichment with larger dots being more significant and color corresponds to the proportion of hypo- (green) and hypermethylated (orange) promoters contributing to each GO term. Top selected GO terms that are unique to or shared between Dnmt3a^ΔIEC and Dnmt3a^fl/fl mice are shown. h Colon Lgr5, Tff3, Axin2, Muc2 mRNA expression levels (qRT-PCR) in crypts isolated from Dnmt3a^ΔIEC and Dnmt3a^fl/fl mice on day 5 (n = 5) and day 12 (n = 7/8). Murine beta-actin was used as housekeeping gene. The values represent mean ± SEM. Statistical analysis was performed using two-tailed t-test with Mann–Whitney correction or one-way ANOVA together with Tukey post hoc test. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.