Leah A. Gates, Bernardo Sgarbi Reis, Peder J. Lund, Matthew R. Paul, Marylene Leboeuf, Annaelle M. Djomo, Zara Nadeem, Mariana Lopes, Francisca N. Vitorino, Gokhan Unlu, Thomas S. Carroll, Kivanç Birsoy, Benjamin A. Garcia, Daniel Mucida, C. David Allis
{"title":"小鼠肠道中的组蛋白丁酰化由微生物群介导,并与基因表达调控有关。","authors":"Leah A. Gates, Bernardo Sgarbi Reis, Peder J. Lund, Matthew R. Paul, Marylene Leboeuf, Annaelle M. Djomo, Zara Nadeem, Mariana Lopes, Francisca N. Vitorino, Gokhan Unlu, Thomas S. Carroll, Kivanç Birsoy, Benjamin A. Garcia, Daniel Mucida, C. David Allis","doi":"10.1038/s42255-024-00992-2","DOIUrl":null,"url":null,"abstract":"Post-translational modifications (PTMs) on histones are a key source of regulation on chromatin through impacting cellular processes, including gene expression1. These PTMs often arise from metabolites and are thus impacted by metabolism and environmental cues2–7. One class of metabolically regulated PTMs are histone acylations, which include histone acetylation, butyrylation, crotonylation and propionylation3,8. As these PTMs can be derived from short-chain fatty acids, which are generated by the commensal microbiota in the intestinal lumen9–11, we aimed to define how microbes impact the host intestinal chromatin landscape, mainly in female mice. Here we show that in addition to acetylation, intestinal epithelial cells from the caecum and distal mouse intestine also harbour high levels of butyrylation and propionylation on lysines 9 and 27 of histone H3. We demonstrate that these acylations are regulated by the microbiota and that histone butyrylation is additionally regulated by the metabolite tributyrin. Tributyrin-regulated gene programmes are correlated with histone butyrylation, which is associated with active gene-regulatory elements and levels of gene expression. Together, our study uncovers a regulatory layer of how the microbiota and metabolites influence the intestinal epithelium through chromatin, demonstrating a physiological setting in which histone acylations are dynamically regulated and associated with gene regulation. Gates et al. show that histone butyrylation and propionylation in the intestinal epithelium are regulated by the gut microbiota and histone butyrylation is associated with gene regulatory programmes.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":null,"pages":null},"PeriodicalIF":18.9000,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Histone butyrylation in the mouse intestine is mediated by the microbiota and associated with regulation of gene expression\",\"authors\":\"Leah A. Gates, Bernardo Sgarbi Reis, Peder J. Lund, Matthew R. Paul, Marylene Leboeuf, Annaelle M. Djomo, Zara Nadeem, Mariana Lopes, Francisca N. Vitorino, Gokhan Unlu, Thomas S. Carroll, Kivanç Birsoy, Benjamin A. Garcia, Daniel Mucida, C. David Allis\",\"doi\":\"10.1038/s42255-024-00992-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Post-translational modifications (PTMs) on histones are a key source of regulation on chromatin through impacting cellular processes, including gene expression1. These PTMs often arise from metabolites and are thus impacted by metabolism and environmental cues2–7. One class of metabolically regulated PTMs are histone acylations, which include histone acetylation, butyrylation, crotonylation and propionylation3,8. As these PTMs can be derived from short-chain fatty acids, which are generated by the commensal microbiota in the intestinal lumen9–11, we aimed to define how microbes impact the host intestinal chromatin landscape, mainly in female mice. Here we show that in addition to acetylation, intestinal epithelial cells from the caecum and distal mouse intestine also harbour high levels of butyrylation and propionylation on lysines 9 and 27 of histone H3. We demonstrate that these acylations are regulated by the microbiota and that histone butyrylation is additionally regulated by the metabolite tributyrin. Tributyrin-regulated gene programmes are correlated with histone butyrylation, which is associated with active gene-regulatory elements and levels of gene expression. Together, our study uncovers a regulatory layer of how the microbiota and metabolites influence the intestinal epithelium through chromatin, demonstrating a physiological setting in which histone acylations are dynamically regulated and associated with gene regulation. 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Histone butyrylation in the mouse intestine is mediated by the microbiota and associated with regulation of gene expression
Post-translational modifications (PTMs) on histones are a key source of regulation on chromatin through impacting cellular processes, including gene expression1. These PTMs often arise from metabolites and are thus impacted by metabolism and environmental cues2–7. One class of metabolically regulated PTMs are histone acylations, which include histone acetylation, butyrylation, crotonylation and propionylation3,8. As these PTMs can be derived from short-chain fatty acids, which are generated by the commensal microbiota in the intestinal lumen9–11, we aimed to define how microbes impact the host intestinal chromatin landscape, mainly in female mice. Here we show that in addition to acetylation, intestinal epithelial cells from the caecum and distal mouse intestine also harbour high levels of butyrylation and propionylation on lysines 9 and 27 of histone H3. We demonstrate that these acylations are regulated by the microbiota and that histone butyrylation is additionally regulated by the metabolite tributyrin. Tributyrin-regulated gene programmes are correlated with histone butyrylation, which is associated with active gene-regulatory elements and levels of gene expression. Together, our study uncovers a regulatory layer of how the microbiota and metabolites influence the intestinal epithelium through chromatin, demonstrating a physiological setting in which histone acylations are dynamically regulated and associated with gene regulation. Gates et al. show that histone butyrylation and propionylation in the intestinal epithelium are regulated by the gut microbiota and histone butyrylation is associated with gene regulatory programmes.
期刊介绍:
Nature Metabolism is a peer-reviewed scientific journal that covers a broad range of topics in metabolism research. It aims to advance the understanding of metabolic and homeostatic processes at a cellular and physiological level. The journal publishes research from various fields, including fundamental cell biology, basic biomedical and translational research, and integrative physiology. It focuses on how cellular metabolism affects cellular function, the physiology and homeostasis of organs and tissues, and the regulation of organismal energy homeostasis. It also investigates the molecular pathophysiology of metabolic diseases such as diabetes and obesity, as well as their treatment. Nature Metabolism follows the standards of other Nature-branded journals, with a dedicated team of professional editors, rigorous peer-review process, high standards of copy-editing and production, swift publication, and editorial independence. The journal has a high impact factor, has a certain influence in the international area, and is deeply concerned and cited by the majority of scholars.