GSE127479
Smarcad1 coordinates innate immunity-linked gene expression in the intestinal epithelium [ATAC-seq]
How intestinal epithelial cells interact with the host immune system and the microbiota and how this is regulated at the gene expression level are critical questions. 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 and colon. Absence of Smarcad1 led to changes in chromatin accessibility and significant changes in histone H3K9me3 but not H3K9me2 over many sites, including many genes that are differentially regulated upon Smarcad1 deletion. Our study demonstrates that an innate immunity response can be coordinated by a chromatin remodelling factor. Overall design: Comparisons between wild type mice and Vil-Cre mediated KO of Smarcad1 in the intestinal epithelium. C57BL/6 background. ATAC-seq performed in triplicates on whole crypt epithelium of the small intestine.