Metabolic Regulation of Gene Expression by Histone Lysine β-Hydroxybutyrylation.
Metabolic Regulation of Gene Expression by Histone Lysine β-Hydroxybutyrylation.
复制标题
DOI：
10.1016/j.molcel.2016.03.036
复制
发表时间：
2016-04-21
期刊：
影响因子：
16
通讯作者：
Zhao Y
中科院分区：
文献类型：
--
作者：
Xie Z;Zhang D;Chung D;Tang Z;Huang H;Dai L;Qi S;Li J;Colak G;Chen Y;Xia C;Peng C;Ruan H;Kirkey M;Wang D;Jensen LM;Kwon OK;Lee S;Pletcher SD;Tan M;Lombard DB;White KP;Zhao H;Li J;Roeder RG;Yang X;Zhao Y
在这里，我们报告了一种基于β-羟丁酸衍生的蛋白质修饰，赖氨酸β-羟丁酰化(KBHb)，作为一种新型的组蛋白标记的鉴定和验证。组蛋白KbHb标记在培养细胞和长期禁食或链脲佐菌素诱导的糖尿病酮症酸中毒小鼠肝脏中β-羟丁酸水平升高时显著诱导。我们总共确定了44个组蛋白Kbhb位点，这一数字与已知的组蛋白乙酰化位点的数量相当。通过CHIP-SEQ和RNA-SEQ分析，我们证明了组蛋白Kbhb是一个富含活性基因启动子的标记，并且饥饿过程中H3K9bhb水平的增加与饥饿反应代谢途径中上调的基因有关。因此，组蛋白β-羟丁酰化反应代表了一种新的表观遗传调节标记，它将代谢与基因表达结合起来，为研究染色质调节和β-羟丁酸在包括糖尿病、癫痫和肿瘤等重要人类病理生理状态下的不同功能提供了新的途径。
Here we report the identification and verification of a β-hydroxybutyrate-derived protein modification, lysine β-hydroxybutyrylation (Kbhb), as a new type of histone mark. Histone Kbhb marks are dramatically induced in response to elevated β-hydroxybutyrate levels in cultured cells, and in livers from mice subjected to prolonged fasting or streptozotocin-induced diabetic ketoacidosis. In total, we identified 44 histone Kbhb sites, a figure comparable to the known number of histone acetylation sites. By ChIP-seq and RNA-seq analysis, we demonstrate that histone Kbhb is a mark enriched in active gene promoters, and that the increased H3K9bhb levels that occur during starvation are associated with genes up-regulated in starvation-responsive metabolic pathways. Histone β-hydroxybutyrylation thus represents a new epigenetic regulatory mark that couples metabolism to gene expression, offering a new avenue to study chromatin regulation and the diverse functions of β-hydroxybutyrate in the context of important human pathophysiological states, including diabetes, epilepsy, and neoplasia.
登录
查看更多内容
影响因子：
29
作者：
Ruan HB;Han X;Li MD;Singh JP;Qian K;Azarhoush S;Zhao L;Bennett AM;Samuel VT;Wu J;Yates JR 3rd;Yang X
通讯作者：
Yang X
影响因子：
64.5
作者：
Kaelin WG Jr;McKnight SL
通讯作者：
McKnight SL
DOI：
10.1126/science.1227166
发表时间：
2013-01-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Shimazu T;Hirschey MD;Newman J;He W;Shirakawa K;Le Moan N;Grueter CA;Lim H;Saunders LR;Stevens RD;Newgard CB;Farese RV Jr;de Cabo R;Ulrich S;Akassoglou K;Verdin E
通讯作者：
Verdin E
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Huang H;Sabari BR;Garcia BA;Allis CD;Zhao Y
通讯作者：
Zhao Y