Smarcad1 coordinates innate immunity-linked gene expression in the intestinal epithelium [wCO RNA-seq]

Smarcad1 is one of the most conserved chromatin remodelling factors, from yeast to human, with suggested functions in gene silencing, heterochromatin maintenance and genome stability. However, its role in tissue function is poorly understood. As this factor is highly expressed in the stem- and proliferative zone in the intestinal epithelium, we explored the role of this factor in this tissue. Specific deletion of Smarcad1 in the intestinal epithelium led to colitis resistance in the dextran sodium sulphate colitis model. Intestine tissue-specific deletion of Smarcad1 resulted in notable changes in gene expression in the small intestine, colon and organoids from small intestine. Strikingly, we found an increase of expression of several genes linked to innate immunity. Our study demonstrates that an innate immunity response can be coordinated by a chromatin remodelling factor. It highlights the role of intestinal epithelial cells in the colitis response and we identified candidate members of the gut microbiome that elicit an epithelial Smarcad1-dependent colitis response. Overall design: Compared genotypes: wild type mice and Vil-Cre mediated KO of Smarcad1 in the small intestinal epithelium. C57BL/6 background. Enriched microbiota by bedding transfer from another SPF-facility. RNA-seq performed on whole small intestinal tissue. Triplicates for untreated control samples, 5 replicates for DSS-induced colitis samples. 16 samples total.