Reprogramming of H3K9bhb at regulatory elements is a key feature of fasting in the small intestine
Christopher Terranova, Kristina M. Stemler, Praveen Barrodia, Sabrina L. Jeter-Jones, Zhongqi Ge, Marimar de la Cruz Bonilla, Ayush T. Raman, Chia‐Wei Cheng, Kendra Allton, Emre Arslan, Ömer Yılmaz, Michelle Barton, Kunal Rai, Helen Piwnica‐Worms
Abstract
stem cell-enriched epithelial spheroids treated with β-OHB in vitro. Combinatorial chromatin state analysis reveals that H3K9bhb is associated with active chromatin states and that fasting enriches for an H3K9bhb-H3K27ac signature at active metabolic gene promoters and distal enhancer elements. Intestinal knockout of Hmgcs2 results in marked loss of H3K9bhb-associated loci, suggesting that local production of β-OHB is responsible for chromatin reprogramming within the SI crypt. We conclude that modulation of H3K9bhb in SI crypts is a key gene regulatory event in response to fasting.