science20130111-8

来自美国哈佛医学院的研究人员发现小鼠胚胎干细胞中不同寻常的苏氨酸代谢能够影响组蛋白的甲基化水平,进而调控干细胞的基因重组。这项研究揭示了代谢与表观遗传学的关联特点。

-2013年1月11日《科学》

中文翻译


【题目】苏氨酸的代谢影响S-腺苷甲硫氨酸与组蛋白甲基化的水平

【译文】苏氨酸是小鼠胚胎干细胞(mESCs)发挥其多能性所需的唯一的关键氨基酸,但相关的详细机制还不清楚。本研究在多能干细胞中发现苏氨酸和S-腺苷甲硫氨酸(SAM)的代谢耦合,共同调节组蛋白的甲基化。利用同位素标记mESCs,本研究发现苏氨酸为SAM合成所需的前体物质——甘氨酸和乙酰辅酶A的来源提供大量的分子片段。mESCs的细胞培养基中缺乏苏氨酸或mESCs中缺失苏氨酸脱氢酶(Tdh),会降低组蛋白H3赖氨酸4的三甲基化水平,导致mESCs缓慢生长且加速分化。因此,大量的SAM似乎能够影响组蛋白H3赖氨酸4的三甲基化水平,而这可能是一种新型调控机制,即通过调节可能影响干细胞命运的代谢途径来调控干细胞的发育。

英文原稿


[Title]: Influence of Threonine Metabolism on S-Adenosylmethionine and Histone Methylation   

[Authors]: Ng Shyh-Chang, Jason W. Locasale, Costas A. Lyssiotis, Yuxiang Zheng, Ren Yi Teo, Sutheera Ratanasirintrawoot, Jin Zhang, Tamer Onder, Juli J. Unternaehrer, Hao Zhu, John M. Asara, George Q. Daley, and Lewis C. Cantley

[Abstract]: Threonine is the only amino acid critically required for the pluripotency of mouse embryonic stem cells (mESCs), but the detailed mechanism remains unclear. We found that threonine and S-adenosylmethionine (SAM) metabolism are coupled in pluripotent stem cells, resulting in regulation of histone methylation. Isotope labeling of mESCs revealed that threonine provides a substantial fraction of both the cellular glycine and the acetyl–coenzyme A (CoA) needed for SAM synthesis. Depletion of threonine from the culture medium or threonine dehydrogenase (Tdh) from mESCs decreased accumulation of SAM and decreased trimethylation of histone H3 lysine 4 (H3K4me3), leading to slowed growth and increased differentiation. Thus, abundance of SAM appears to influence H3K4me3, providing a possible mechanism by which modulation of a metabolic pathway might influence stem cell fate.

原文地址

http://www.sciencemag.org/content/339/6116/222.short

本站声明: 生物文库所有文章欢迎转载,所有文章未说明,均属于原创,转载均请注明出处。
本文链接: http://www.bioku.cn/201303/science-threonine-metabolism-s-adenosylmethionine-histone-methylation/
版权所有: 生物文库 - 生物医学、生物技术核心期刊文摘

留言


一 − 1 =


沪ICP备12028140号
点击这里给我发消息   点击这里给我发消息