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Cell Metab.：韓敬東等發現組蛋白修飾對衰老調控機制

作者：admin 來源：科學時報發布時間： 2011-08-21 13:22　瀏覽次數：

購買進口儀器、試劑和耗材——就在始于2001年的畢特博生物 www.chenzhangqi.cn

近日，中科院遺傳與發育生物學研究所韓敬東實驗室的組蛋白修飾對衰老的調控機制研究，作為封面文章在線發表于國際著名學術期刊《細胞—代謝》（Cell Metabolism）。該雜志同期以preview的形式對這項研究給予了高度評價，認為：“文章的實驗證據表明，重新建立表觀遺傳狀態為延緩衰老甚至逆轉衰老提供了可能性，這是重要的發現。”

這項研究通過生物化學、分子生物學、遺傳學和系統生物學相結合的方法，發現組蛋白H3K27me2/3去甲基酶UTX-1/UTX對衰老發揮了重要的調控作用。在秀麗線蟲中，該基因的雜合突變體及野生型的RNAi敲降后都能極大地延長線蟲壽命，使其抗逆性也大大加強。遺傳學分析發現其功能依賴于胰島素樣信號通路。這種通過重新建立組蛋白修飾模式的作用方式，揭示了細胞的重編程在抑制衰老過程中的重要作用，并提示其作用機制在哺乳動物細胞中同樣存在。

該研究首次報道了通過體細胞發揮功能的組蛋白修飾基因對衰老這一重要生物學過程的調控作用，加深了對表觀遺傳功能的認識，并為新型抗衰老藥物的研發提供了潛在的靶點。

因為這項工作是由中國本土實驗室完成的，封面圖片也設計成中國風格。

doi:10.1016/j.cmet.2011.07.001
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Histone Demethylase UTX-1 Regulates C. elegans Life Span by Targeting the Insulin/IGF-1 Signaling Pathway

Chunyu Jin, Jing Li, Christopher D. Green, Xiaoming Yu, Xia Tang, Dali Han, Bo Xian, Dan Wang, Xinxin Huang, Xiongwen Cao, Zheng Yan, Lei Hou, Jiancheng Liu, Nicholas Shukeir, Philipp Khaitovich, Charlie D. Chen, Hong Zhang, Thomas Jenuwein, Jing-Dong J. Han

Epigenetic modifications are thought to be important for gene expression changes during development and aging. However, besides the Sir2 histone deacetylase in somatic tissues and H3K4 trimethylation in germlines, there is scant evidence implicating epigenetic regulations in aging. The insulin/IGF-1 signaling (IIS) pathway is a major life span regulatory pathway. Here, we show that progressive increases in gene expression and loss of H3K27me3 on IIS components are due, at least in part, to increased activity of the H3K27 demethylase UTX-1 during aging. RNAi of the utx-1 gene extended the mean life span of C. elegans by ∼30%, dependent on DAF-16 activity and not additive in daf-2 mutants. The loss of utx-1 increased H3K27me3 on the Igf1r/daf-2 gene and decreased IIS activity, leading to a more “naive” epigenetic state. Like stem cell reprogramming, our results suggest that reestablishment of epigenetic marks lost during aging might help “reset” the developmental age of animal cells.

購買進口儀器、試劑和耗材——就在始于2001年的畢特博生物 www.chenzhangqi.cn

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