Histone H3K9 butyrylation is regulated by dietary fat and stress via an Acyl-CoA dehydrogenase short chain-dependent mechanism.
Histone H3K9 butyrylation is regulated by dietary fat and stress via an Acyl-CoA dehydrogenase short chain-dependent mechanism.
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DOI：
10.1016/j.molmet.2021.101249
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发表时间：
2021-11
影响因子：
8.1
通讯作者：
Abdellatif M
中科院分区：
文献类型：
--
作者：
Yang Z;He M;Austin J;Pfleger J;Abdellatif M
我们以前报道过β-氧化酶存在于细胞核中，靠近转录活性启动子。因此，我们假设脂肪酸中间体丁酰辅酶A是组蛋白丁酰化的底物，其丰度受酰基辅酶A脱氢酶短链（ACADS）调节。本研究的目的是确定H3 K9-丁酰基（H3 K9 Bu）的基因组分布及其通过膳食脂肪、应激和ACADS的调节及其对基因表达的影响。使用全基因组染色质免疫沉淀测序（ChIP-Seq），我们发现H3 K9 Bu在所有转录活性启动子中都是丰富的，而矛盾的是，它在喂食无脂肪与高脂肪饮食的小鼠中最丰富。删除脂肪酸合成酶（FRESH）废除H3 K9 Bu在细胞中保持在富含葡萄糖，但不富含脂肪酸的培养基，这意味着脂肪酸合成碳水化合物取代膳食脂肪作为丁酰辅酶A的来源。高脂饮食诱导ACADS表达增加，同时H3 K9 Bu减少。相反，ACADS的缺失增加了人类细胞和小鼠心脏中的H3 K9 Bu，并逆转了高脂肪和应激诱导的启动子H3 K9 Bu的减少，其丰度与RNA测序显示的应激调节基因表达减少相一致。相反，H3 K9-乙酰基（H3 K9 Ac）丰度受饮食影响最小。启动子H3 K9丁酰化是一种主要的组蛋白修饰，其以ACADS依赖的方式受到高脂肪和应激的负调控，并调节应激调节的基因表达。H3 K9-丁酰基在所有活性启动子处都是丰富的。高脂饮食和压力减少促进剂-H3 K9-丁酰基，但不是H3 K9-乙酰基。从葡萄糖合成脂肪酸替代膳食脂肪作为H3 K9-丁酰基的来源。ACADS的敲除增加H3 K9-丁酰基的水平。启动子-H3 K9-丁酰基与胁迫诱导的基因表达变化呈负相关。
We previously reported that β-oxidation enzymes are present in the nucleus in close proximity to transcriptionally active promoters. Thus, we hypothesized that the fatty acid intermediate, butyryl-CoA, is the substrate for histone butyrylation and its abundance is regulated by acyl-CoA dehydrogenase short chain (ACADS). The objective of this study was to determine the genomic distribution of H3K9-butyryl (H3K9Bu) and its regulation by dietary fat, stress, and ACADS and its impact on gene expression. Using genome-wide chromatin immunoprecipitation-sequencing (ChIP–Seq), we show that H3K9Bu is abundant at all transcriptionally active promoters, where, paradoxically, it is most enriched in mice fed a fat-free vs high-fat diet. Deletion of fatty acid synthetase (FASN) abolished H3K9Bu in cells maintained in a glucose-rich but not fatty acid-rich medium, signifying that fatty acid synthesis from carbohydrates substitutes for dietary fat as a source of butyryl-CoA. A high-fat diet induced an increase in ACADS expression that accompanied the decrease in H3K9Bu. Conversely, the deletion of ACADS increased H3K9Bu in human cells and mouse hearts and reversed high-fat- and stress-induced reduction in promoter-H3K9Bu, whose abundance coincided with diminished stress-regulated gene expression as revealed by RNA sequencing. In contrast, H3K9-acetyl (H3K9Ac) abundance was minimally impacted by diet. Promoter H3K9 butyrylation is a major histone modification that is negatively regulated by high fat and stress in an ACADS-dependent fashion and moderates stress-regulated gene expression. H3K9-butyryl is abundant at all active promoters. A high-fat diet and stress reduce promoter-H3K9-butyryl but not H3K9-acetyl. Fatty acid synthesis from glucose substitutes for dietary fat as a source of H3K9-butyryl. Knockout of ACADS increases levels of H3K9-butyryl. Promoter-H3K9-butyryl inversely correlates with stress-induced changes in gene expression.
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DOI：
10.1073/pnas.48.5.840
发表时间：
1962-01-01
影响因子：
11.1
作者：
LENNARZ, WJ;LIGHT, RJ;BLOCH, K
通讯作者：
BLOCH, K
影响因子：
20.1
作者：
Rane S;He M;Sayed D;Vashistha H;Malhotra A;Sadoshima J;Vatner DE;Vatner SF;Abdellatif M
通讯作者：
Abdellatif M
DOI：
10.1146/annurev-cellbio-100814-125544
发表时间：
2015
影响因子：
11.3
作者：
Janke R;Dodson AE;Rine J
通讯作者：
Rine J
乙酰化和甲基化相关的表观遗传蛋白在其靶标的背景下。
影响因子：
3.5
作者：
Javaid N;Choi S
通讯作者：
Choi S
DOI：
10.1093/bioinformatics/btp472
发表时间：
2009-10-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Nicol JW;Helt GA;Blanchard SG Jr;Raja A;Loraine AE
通讯作者：
Loraine AE