Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases.
Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases.
复制标题
DOI：
10.1038/s41467-017-02651-5
复制
发表时间：
2018-01-09
影响因子：
16.6
通讯作者：
Varga-Weisz P
中科院分区：
文献类型：
--
作者：
Fellows R;Denizot J;Stellato C;Cuomo A;Jain P;Stoyanova E;Balázsi S;Hajnády Z;Liebert A;Kazakevych J;Blackburn H;Corrêa RO;Fachi JL;Sato FT;Ribeiro WR;Ferreira CM;Perée H;Spagnuolo M;Mattiuz R;Matolcsi C;Guedes J;Clark J;Veldhoen M;Bonaldi T;Vinolo MAR;Varga-Weisz P
最近发现的组蛋白翻译后修饰巴豆化将细胞代谢与基因调控联系起来。它的调节和组织特异性功能知之甚少。我们研究了组蛋白在肠上皮细胞中的巴豆化，发现组蛋白H3在赖氨酸18处的巴豆化是一种令人惊讶的丰富的修饰，在小肠隐窝和结肠中，并且与基因调控有关。我们发现，这种修饰在细胞周期中是高度动态和受调控的。我们确定I类组蛋白去乙酰基酶HDAC1、HDAC2和HDAC3是组蛋白去乙酰化的主要执行者。我们发现，已知的HDAC抑制剂，包括肠道微生物群衍生的丁酸盐，会影响组蛋白去内酯。与此一致，我们发现肠道微生物区系的枯竭导致结肠组蛋白巴豆化的全球变化。我们的结果表明，组蛋白巴豆化至少部分通过短链脂肪酸和HDAC将染色质与肠道微生物区系连接起来。组蛋白翻译后修饰是已知的基因表达的关键调节因子。在这里，作者表征了肠上皮细胞中组蛋白H3赖氨酸18的组蛋白巴豆化，并发现它是一个在HDAC脱乙酰酶的调控下高度动态的细胞周期调节的标志。
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. Histone post-translational modifications are known key regulators of gene expression. Here, the authors characterize histone crotonylation at histone H3 lysine 18 in intestinal epithelia and find that it is a highly dynamic cell cycle regulated mark under the regulation of the HDAC deacetylases.
登录
查看更多内容
影响因子：
5.2
作者：
Mendes E;Acetturi BG;Thomas AM;Martins FDS;Crisma AR;Murata G;Braga TT;Camâra NOS;Franco ALDS;Setubal JC;Ribeiro WR;Valduga CJ;Curi R;Dias-Neto E;Tavares-de-Lima W;Ferreira CM
通讯作者：
Ferreira CM
影响因子：
5.4
作者：
Li Y;Seto E
通讯作者：
Seto E
影响因子：
29
作者：
Donohoe DR;Garge N;Zhang X;Sun W;O'Connell TM;Bunger MK;Bultman SJ
通讯作者：
Bultman SJ
影响因子：
7
作者：
Jung, Hye Ryung;Pasini, Diego;Jensen, Ole N.
通讯作者：
Jensen, Ole N.
影响因子：
16
作者：
Jasencakova, Zuzana;Scharf, Annette N. D.;Groth, Anja
通讯作者：
Groth, Anja