Histone butyrylation in the mouse intestine is mediated by the microbiota and associated with regulation of gene expression.
Histone butyrylation in the mouse intestine is mediated by the microbiota and associated with regulation of gene expression.
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DOI：
10.1038/s42255-024-00992-2
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发表时间：
2024-02
影响因子：
20.8
通讯作者：
Leah A. Gates;B. Reis;P. Lund;M. Paul;Marylene Leboeuf;Annaelle M. Djomo;Zara Nadeem;Mariana Lopes;Francisca N Vitorino;G. Unlu;Thomas S. Carroll;Kıvanç Birsoy;Benjamin A. Garcia;D. Mucida;C. D. Allis
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作者：
Leah A. Gates;B. Reis;P. Lund;M. Paul;Marylene Leboeuf;Annaelle M. Djomo;Zara Nadeem;Mariana Lopes;Francisca N Vitorino;G. Unlu;Thomas S. Carroll;Kıvanç Birsoy;Benjamin A. Garcia;D. Mucida;C. D. Allis
组蛋白的翻译后修饰(PTM)是通过影响包括基因表达在内的细胞过程来调节染色质的关键来源。这些PTM通常来自代谢物，因此受到新陈代谢和环境提示的影响。组蛋白酰化是一类代谢调节的组蛋白酰化反应，包括组蛋白乙酰化、丁酰化、巴豆化和丙酰化。由于这些PTM可以来自短链脂肪酸，而短链脂肪酸是由肠腔中的共生微生物群产生的，我们的目标是定义微生物如何影响宿主肠道的染色质景观，主要是在雌性小鼠身上。在这里，我们表明，除了乙酰化，来自盲肠和远端小鼠肠道的肠上皮细胞在组蛋白H3的赖氨酸9和27上也有高水平的丁酰化和丙酰化。我们证明，这些酰化反应受微生物区系调节，组蛋白丁酰化反应还受代谢物三丁酸甘油酯的调节。三酸甘油酯调节的基因程序与组蛋白丁酰化反应相关，组蛋白丁酰化反应与活跃的基因调节元件和基因表达水平有关。总之，我们的研究揭示了微生物区系和代谢物如何通过染色质影响肠上皮的调节层，展示了组蛋白酰化被动态调控并与基因调控相关的生理环境。
Post-translational modifications (PTMs) on histones are a key source of regulation on chromatin through impacting cellular processes, including gene expression. These PTMs often arise from metabolites and are thus impacted by metabolism and environmental cues, , , , –. One class of metabolically regulated PTMs are histone acylations, which include histone acetylation, butyrylation, crotonylation and propionylation,. As these PTMs can be derived from short-chain fatty acids, which are generated by the commensal microbiota in the intestinal lumen, –, 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.