Identification of lysine isobutyrylation as a new histone modification mark.
Identification of lysine isobutyrylation as a new histone modification mark.
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DOI：
10.1093/nar/gkaa1176
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发表时间：
2021-01-11
影响因子：
14.9
通讯作者：
Zheng YG
中科院分区：
文献类型：
--
作者：
Zhu Z;Han Z;Halabelian L;Yang X;Ding J;Zhang N;Ngo L;Song J;Zeng H;He M;Zhao Y;Arrowsmith CH;Luo M;Bartlett MG;Zheng YG
真核生物蛋白质中赖氨酸残基的短链酰化被认为是重要的翻译后化学修饰（PTMs），调节着从转录、细胞周期、代谢到信号转导等细胞过程。赖氨酸丁酰化最初被发现是一种正常的直链丁酰化（Knbu-Butyrylation）。在这里，我们报告其结构异构体，支链丁酰化，即赖氨酸异丁酰化（Kibu），存在作为一个新的PTM的核组蛋白。独特的是，异丁酰辅酶A来源于缬氨酸催化剂和支链脂肪酸氧化，这与正丁酰辅酶A的代谢不同。几种组蛋白乙酰转移酶被发现具有赖氨酸异丁酰转移酶活性，特别是p300和HAT 1。转染和蛋白质印迹实验表明，p300调节细胞中组蛋白异丁酰化水平。我们解析了HAT 1与异丁酰辅酶A复合物的X射线晶体结构，从而在原子水平上深入了解HAT催化的异丁酰化。RNA-Seq分析显示，异丁酸酯极大地影响了与许多关键生物学途径相关的基因的表达。总之，我们的研究结果将Kibu确定为组蛋白中的一种新型化学修饰标记，并表明其在调节表观遗传学和细胞生理学方面的广泛作用。
Short-chain acylations of lysine residues in eukaryotic proteins are recognized as essential posttranslational chemical modifications (PTMs) that regulate cellular processes from transcription, cell cycle, metabolism, to signal transduction. Lysine butyrylation was initially discovered as a normal straight chain butyrylation (Knbu). Here we report its structural isomer, branched chain butyrylation, i.e. lysine isobutyrylation (Kibu), existing as a new PTM on nuclear histones. Uniquely, isobutyryl-CoA is derived from valine catabolism and branched chain fatty acid oxidation which is distinct from the metabolism of n-butyryl-CoA. Several histone acetyltransferases were found to possess lysine isobutyryltransferase activity in vitro, especially p300 and HAT1. Transfection and western blot experiments showed that p300 regulated histone isobutyrylation levels in the cell. We resolved the X-ray crystal structures of HAT1 in complex with isobutyryl-CoA that gleaned an atomic level insight into HAT-catalyzed isobutyrylation. RNA-Seq profiling revealed that isobutyrate greatly affected the expression of genes associated with many pivotal biological pathways. Together, our findings identify Kibu as a novel chemical modification mark in histones and suggest its extensive role in regulating epigenetics and cellular physiology.
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影响因子：
29
作者：
Lee JV;Carrer A;Shah S;Snyder NW;Wei S;Venneti S;Worth AJ;Yuan ZF;Lim HW;Liu S;Jackson E;Aiello NM;Haas NB;Rebbeck TR;Judkins A;Won KJ;Chodosh LA;Garcia BA;Stanger BZ;Feldman MD;Blair IA;Wellen KE
通讯作者：
Wellen KE
影响因子：
5.7
作者：
Flynn, E. Megan;Huang, Oscar W.;Cochran, Andrea G.
通讯作者：
Cochran, Andrea G.
影响因子：
64.8
作者：
Lasko LM;Jakob CG;Edalji RP;Qiu W;Montgomery D;Digiammarino EL;Hansen TM;Risi RM;Frey R;Manaves V;Shaw B;Algire M;Hessler P;Lam LT;Uziel T;Faivre E;Ferguson D;Buchanan FG;Martin RL;Torrent M;Chiang GG;Karukurichi K;Langston JW;Weinert BT;Choudhary C;de Vries P;Van Drie JH;McElligott D;Kesicki E;Marmorstein R;Sun C;Cole PA;Rosenberg SH;Michaelides MR;Lai A;Bromberg KD
通讯作者：
Bromberg KD
一种用于蛋白质共依旋化的化学探针。
影响因子：
15
作者：
Bos J;Muir TW
通讯作者：
Muir TW
影响因子：
8.9
作者：
Grevengoed TJ;Klett EL;Coleman RA
通讯作者：
Coleman RA