Crotonate-activated histone H3K14 crotonylation enhances intestinal regeneration after injury [RNA-seq]

The intestinal epithelium undergoes rapid turnover driven by Lgr5+ intestinal stem cells (ISCs) at the crypt base, and can recover despite ISC loss during damage. However, the role of epigenetic modifications in regulating this regeneration remains unclear. In this study, we report that H3K14 crotonylation (H3K14cr), a vital histone modification mediated by the acyltransferase HBO1, is essential for intestinal regeneration. HBO1 ablation in the intestinal epithelium exacerbates dextran sulfate sodium (DSS)-induced colitis. Overall design: Part1: We performed gene expression analysis with RNA-seq data from control and HBO1 KO small intestinal organoids. Otherwise,to study the function of HBO1 in intestinal regeneration, we analyzed RNA-seq data from control and HBO1 KO colonic epithelial cells derived from DSS-treated mice. Part2: This study aims to characterize transcriptional dynamics during tissue damage and subsequent regeneration. Mice are treated with 3% DSS for 5 days, followed by normal drinking water. Colonic crypts were isolated at the indicated time points for bulk RNA-seq.