Reprogramming of H3K9bhb at regulatory elements is a key feature of fasting in the small intestine.
Reprogramming of H3K9bhb at regulatory elements is a key feature of fasting in the small intestine.
复制标题
H3K9bhb在调节元件处的重编程是小肠中禁食的关键特征。
DOI：
10.1016/j.celrep.2021.110044
复制
发表时间：
2021-11-23
期刊：
影响因子：
8.8
通讯作者：
Piwnica-Worms H
中科院分区：
文献类型：
--
作者：
Terranova CJ;Stemler KM;Barrodia P;Jeter-Jones SL;Ge Z;de la Cruz Bonilla M;Raman A;Cheng CW;Allton KL;Arslan E;Yilmaz ÖH;Barton MC;Rai K;Piwnica-Worms H
β-羟基丁酸 (β-OHB) 是禁食期间重要的代谢能量来源，通过核心组蛋白 H3 和 H4 的赖氨酸 β-羟基丁酰化 (Kbhb) 修饰发挥染色质调节剂的作用。我们报告说，组蛋白 H3 (H3K9bhb) 上的 Kbhb 在禁食期间小肠 (SI) 隐窝中与脂解和生酮代谢途径相关的关键基因子集的近端启动子处富集。在体外用 β-OHB 处理的富含 Lgr5+ 干细胞的上皮球体中观察到类似的 Kbhb 富集。组合染色质状态分析表明，H3K9bhb 与活跃的染色质状态相关，并且禁食会丰富活跃代谢基因启动子和远端增强子元件处的 H3K9bhb-H3K27ac 特征。 Hmgcs2 的肠道敲除导致 H3K9bhb 相关基因座的显着丢失，这表明 β-OHB 的局部产生负责 SI 隐窝内的染色质重编程。我们得出结论，SI 隐窝中 H3K9bhb 的调节是响应禁食的关键基因调控事件。特拉诺瓦等人。证明禁食会诱导小肠 (SI) 隐窝细胞产生 HMGCS2 和 β-羟基丁酸。这导致 H3K9bhb 在隐窝上皮细胞中关键代谢基因的调节区域内富集。肠道 Hmgcs2 的缺失会损害 H3K9bhb 富集并影响 H3K9bhb 相关代谢基因程序的表达。
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. Terranova et al. demonstrate that fasting induces production of HMGCS2 and β-hydroxybutyrate in small intestine (SI) crypt cells. This causes enrichment of H3K9bhb within regulatory regions of critical metabolic genes in crypt epithelial cells. Loss of intestinal Hmgcs2 impairs H3K9bhb enrichment and affects expression of H3K9bhb-associated metabolic gene programs.
登录
查看更多内容
影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
64.5
作者：
Guenther, Matthew G.;Levine, Stuart S.;Young, Richard A.
通讯作者：
Young, Richard A.
影响因子：
4.6
作者：
de la Cruz Bonilla M;Stemler KM;Taniguchi CM;Piwnica-Worms H
通讯作者：
Piwnica-Worms H
影响因子：
4.8
作者：
Hakvoort, Theodorus B. M.;Moerland, Perry D.;Sokolovic, Milka
通讯作者：
Sokolovic, Milka