The obesity-associated Fto gene is a transcriptional coactivator.
The obesity-associated Fto gene is a transcriptional coactivator.
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DOI：
10.1016/j.bbrc.2010.09.064
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发表时间：
2010-10-22
影响因子：
3.1
通讯作者：
Chin, Khew-Voon
中科院分区：
文献类型：
--
作者：
Wu, Qiong;Saunders, Rudel A.;Szkudlarek-Mikho, Maria;de la Serna, Ivana;Chin, Khew-Voon
在几个全基因组关联扫描中，脂肪量和肥胖相关的FTO基因已被证明与人类肥胖相关。体外研究表明，Fto可能作为单链DNA去甲基化酶发挥作用。此外，同源重组靶向敲除小鼠中的Fto导致生长迟缓、白色脂肪组织的损失、以及增加的能量代谢和全身交感神经激活。尽管有这些密集的研究，Fto的确切功能仍然不清楚。在这里，我们表明，Fto是一种转录辅激活因子，增强了反式激活潜力的CCAAT/增强子结合蛋白（C/EBP）从未甲基化以及甲基化抑制的基因启动子。Fto也表现出核酸酶活性。我们进一步表明，Fto增强了C/EBP与未甲基化和甲基化DNA的结合。FTO在调节C/EBP对脂肪形成的转录调控中的共激活剂作用与FTO缺陷小鼠脂肪组织的时间进行性损失一致，从而表明FTO在脂肪组织的发育和维持的表观遗传调控中的作用。FTO如何激活甲基抑制基因的转录需要进一步研究。
The fat mass and obesity associated, FTO, gene has been shown to be associated with obesity in human in several genome-wide association scans. In vitro studies suggest that Fto may function as a single-stranded DNA demethylase. In addition, homologous recombination-targeted knockout of Fto in mice resulted in growth retardation, loss of white adipose tissue, and increase energy metabolism and systemic sympathetic activation. Despite these intense investigations, the exact function of Fto remains unclear. We show here that Fto is a transcriptional coactivator that enhances the transactivation potential of the CCAAT/enhancer binding proteins (C/EBPs) from unmethylated as well as methylation-inhibited gene promoters. Fto also exhibits nuclease activity. We showed further that Fto enhances the binding C/EBP to unmethylated and methylated DNA. The coactivator role of FTO in modulating the transcriptional regulation of adipogenesis by C/EBPs is consistent with the temporal progressive loss of adipose tissue in the Fto-deficient mice, thus suggesting a role for Fto in the epigenetic regulation of the development and maintenance of fat tissue. How FTO reactivates transcription from methyl-repressed gene needs to be further investigated.
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影响因子：
9.7
作者：
Finkelstein, Eric A.;Trogdon, Justin G.;Dietz, William
通讯作者：
Dietz, William
通过小鼠和人 FTO 对单链 DNA 和 RNA 中的 3-甲基胸腺嘧啶和 3-甲基尿嘧啶进行氧化去甲基化。
影响因子：
3.5
作者：
Jia, Guifang;Yang, Cai-Guang;Yang, Shangdong;Jian, Xing;Yi, Chengqi;Zhou, Zhiqiang;He, Chuan
通讯作者：
He, Chuan
影响因子：
56.9
作者：
Cooper, PK;Nouspikel, T;Leadon, SA
通讯作者：
Leadon, SA
DOI：
10.1126/science.1151710
发表时间：
2007-11-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gerken T;Girard CA;Tung YC;Webby CJ;Saudek V;Hewitson KS;Yeo GS;McDonough MA;Cunliffe S;McNeill LA;Galvanovskis J;Rorsman P;Robins P;Prieur X;Coll AP;Ma M;Jovanovic Z;Farooqi IS;Sedgwick B;Barroso I;Lindahl T;Ponting CP;Ashcroft FM;O'Rahilly S;Schofield CJ
通讯作者：
Schofield CJ
影响因子：
56.9
作者：
Frayling, Timothy M.;Timpson, Nicholas J.;McCarthy, Mark I.
通讯作者：
McCarthy, Mark I.