Fellows Rachel, Denizot Jérémy, Stellato Claudia, Cuomo Alessandro, Jain Payal, Stoyanova Elena, Balázsi Szabina, Hajnády Zoltán, Liebert Anke, Kazakevych Juri, Blackburn Hector, Corrêa Renan Oliveira, Fachi José Luís, Sato Fabio Takeo, Ribeiro Willian R, Ferreira Caroline Marcantonio, Perée Hélène, Spagnuolo Mariangela, Mattiuz Raphaël, Matolcsi Csaba, Guedes Joana, Clark Jonathan, Veldhoen Marc, Bonaldi Tiziana, Vinolo Marco Aurélio Ramirez, Varga-Weisz Patrick
Nuclear Dynamics, Babraham Institute, Cambridge, CB22 3AT, UK.
Université Clermont Auvergne, Inserm U1071, INRA USC2018, M2iSH, Clermont-Ferrand, F-63000, France.
Nat Commun. 2018 Jan 9;9(1):105. doi: 10.1038/s41467-017-02651-5.
The recently discovered histone post-translational modification crotonylation connects cellular metabolism to gene regulation. Its regulation and tissue-specific functions are poorly understood. We characterize histone crotonylation in intestinal epithelia and find that histone H3 crotonylation at lysine 18 is a surprisingly abundant modification in the small intestine crypt and colon, and is linked to gene regulation. We show that this modification is highly dynamic and regulated during the cell cycle. We identify class I histone deacetylases, HDAC1, HDAC2, and HDAC3, as major executors of histone decrotonylation. We show that known HDAC inhibitors, including the gut microbiota-derived butyrate, affect histone decrotonylation. Consistent with this, we find that depletion of the gut microbiota leads to a global change in histone crotonylation in the colon. Our results suggest that histone crotonylation connects chromatin to the gut microbiota, at least in part, via short-chain fatty acids and HDACs.
最近发现的组蛋白翻译后修饰巴豆酰化将细胞代谢与基因调控联系起来。人们对其调控机制和组织特异性功能了解甚少。我们对肠道上皮中的组蛋白巴豆酰化进行了表征，发现赖氨酸18处的组蛋白H3巴豆酰化在小肠隐窝和结肠中是一种出人意料的丰富修饰，并且与基因调控有关。我们表明这种修饰在细胞周期中高度动态且受调控。我们确定I类组蛋白去乙酰化酶HDAC1、HDAC2和HDAC3是组蛋白去巴豆酰化的主要执行者。我们表明已知的HDAC抑制剂，包括肠道微生物群衍生的丁酸盐，会影响组蛋白去巴豆酰化。与此一致，我们发现肠道微生物群的缺失会导致结肠中组蛋白巴豆酰化的全局变化。我们的结果表明，组蛋白巴豆酰化至少部分地通过短链脂肪酸和HDAC将染色质与肠道微生物群联系起来。
