DNA methyltransferase 3A controls intestinal epithelial barrier function and regeneration in the colon.

ABSTRACT: Genetic variants in the DNA methyltransferase 3 A (DNMT3A) locus have been associated with inflammatory bowel disease (IBD). DNMT3A is part of the epigenetic machinery physiologically involved in DNA methylation. We show that DNMT3A plays a critical role in maintaining intestinal homeostasis and gut barrier function. DNMT3A expression is downregulated in intestinal epithelial cells from IBD patients and upon tumor necrosis factor treatment in murine intestinal organoids. Ablation of DNMT3A in Caco-2 cells results in global DNA hypomethylation, which is linked to impaired regenerative capacity, transepithelial resistance and intercellular junction formation. Genetic deletion of Dnmt3a in intestinal epithelial cells (Dnmt3a^ΔIEC) in mice confirms the phenotype of an altered epithel

SUBMITTER: Fazio A 

PROVIDER: S-EPMC9587301 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature