Reprogramming of H3K9bhb at regulatory elements is a key feature of fasting in the small intestine
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Description
Published version
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6.87 MB
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Author(s)
Terranova, Christopher J
Stemler, Kristina M
Barrodia, Praveen
Jeter-Jones, Sabrina L
Ge, Zhongqi
de la Cruz Bonilla, Marimar
Raman, Ayush
Cheng, Chia-Wei
Allton, Kendra L
Arslan, Emre
Date Issued
2021
Journal
Cell Reports
Publisher
Elsevier BV
Citation
Terranova, Christopher J, Stemler, Kristina M, Barrodia, Praveen, Jeter-Jones, Sabrina L, Ge, Zhongqi et al. 2021. "Reprogramming of H3K9bhb at regulatory elements is a key feature of fasting in the small intestine." Cell Reports, 37 (8).
Version
Final published version
Abstract
β-hydroxybutyrate (β-OHB) is an essential metabolic energy source during fasting and functions as a chromatin regulator by lysine β-hydroxybutyrylation (Kbhb) modification of the core histones H3 and H4. We report that Kbhb on histone H3 (H3K9bhb) is enriched at proximal promoters of critical gene subsets associated with lipolytic and ketogenic metabolic pathways in small intestine (SI) crypts during fasting. Similar Kbhb enrichment is observed in Lgr5+ 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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.CELREP.2021.110044
