Characterization of histone acylations links chromatin modifications with metabolism.
Characterization of histone acylations links chromatin modifications with metabolism.
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DOI：
10.1038/s41467-017-01384-9
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发表时间：
2017-10-26
影响因子：
16.6
通讯作者：
Garcia BA
中科院分区：
文献类型：
--
作者：
Simithy J;Sidoli S;Yuan ZF;Coradin M;Bhanu NV;Marchione DM;Klein BJ;Bazilevsky GA;McCullough CE;Magin RS;Kutateladze TG;Snyder NW;Marmorstein R;Garcia BA
在过去的十年中，人们发现了许多组蛋白酰基翻译后修饰（acyl-PTM），其功能意义仍在深入研究中。在这里，我们使用高分辨率质谱法在体内和体外酶测定后准确定量八种酰基-PTM。我们评估了七种组蛋白乙酰转移酶 (HAT) 在体外使用短链酰基辅酶 A 供体催化组蛋白酰化的能力，证明它们对较大酰基辅酶 A 的效率较低。我们还观察到酰基辅酶A可以通过非酶机制酰化组蛋白。使用综合代谢组学和蛋白质组学方法，我们在酰基辅酶A的丰度与其相应的酰基翻译后修饰之间实现了高度相关性（R 2 > 0.99）。此外，我们观察到在核反应中补充酰基辅酶A后，组蛋白酰基-PTM丰度呈剂量依赖性增加。这项研究对很少研究的低丰度组蛋白标记进行了全面分析，揭示了酰基辅酶A的浓度通过酶促和非酶促机制影响组蛋白酰基-PTM丰度。已鉴定出许多与乙酰化相关的组蛋白赖氨酸修饰，但其功能意义尚不清楚。在这里，作者使用体外和体内测定来表征八种酰基组蛋白翻译后修饰，并将它们的丰度与代谢联系起来。
Over the last decade, numerous histone acyl post-translational modifications (acyl-PTMs) have been discovered, of which the functional significance is still under intense study. Here, we use high-resolution mass spectrometry to accurately quantify eight acyl-PTMs in vivo and after in vitro enzymatic assays. We assess the ability of seven histone acetyltransferases (HATs) to catalyze acylations on histones in vitro using short-chain acyl-CoA donors, proving that they are less efficient towards larger acyl-CoAs. We also observe that acyl-CoAs can acylate histones through non-enzymatic mechanisms. Using integrated metabolomic and proteomic approaches, we achieve high correlation (R 2 > 0.99) between the abundance of acyl-CoAs and their corresponding acyl-PTMs. Moreover, we observe a dose-dependent increase in histone acyl-PTM abundances in response to acyl-CoA supplementation in in nucleo reactions. This study represents a comprehensive profiling of scarcely investigated low-abundance histone marks, revealing that concentrations of acyl-CoAs affect histone acyl-PTM abundances by both enzymatic and non-enzymatic mechanisms. A number of histone lysine modifications related to acetylation have been identified, but their functional significance is unclear. Here, the authors use in vitro and in vivo assays to characterize eight acyl histone post-translational modifications and link their abundance with metabolism.
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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：
16.8
作者：
Liszczak G;Goldberg JM;Foyn H;Petersson EJ;Arnesen T;Marmorstein R
通讯作者：
Marmorstein R
影响因子：
64.5
作者：
Kaelin WG Jr;McKnight SL
通讯作者：
McKnight SL
DOI：
10.1146/annurev-cellbio-100814-125544
发表时间：
2015
影响因子：
11.3
作者：
Janke R;Dodson AE;Rine J
通讯作者：
Rine J
影响因子：
14.8
作者：
Bracha, Abigail L.;Ramanathan, Arvind;Huang, Sui;Ingber, Donald E.;Schreiber, Stuart L.
通讯作者：
Schreiber, Stuart L.