Reprogramming of H3K9bhb at regulatory elements is a key feature of fasting in the small intestine.

Autor:	Terranova CJ; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Stemler KM; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Barrodia P; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Jeter-Jones SL; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Ge Z; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., de la Cruz Bonilla M; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Raman A; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Epigenomics Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Cheng CW; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA., Allton KL; Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Arslan E; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Yilmaz ÖH; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA., Barton MC; Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Rai K; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: krai@mdanderson.org., Piwnica-Worms H; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: hpiwnica-worms@mdanderson.org.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Nov 23; Vol. 37 (8), pp. 110044.
DOI:	10.1016/j.celrep.2021.110044
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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