Crotonate-activated histone H3K14 crotonylation enhances intestinal regeneration after injury [ChIP-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. To study how HBO1 regulates ISC and fetal genes expression, the control and HBO1 KO colonic crypts were subject to CUT&Tag and ChIP-seq with HBO1, H3K14ac and H3K14cr antibodies.Otherwise, the control and HBO1 KO mice were treated with 3% DSS, and the crypts were isolated at day 3 for ATAC-seq.