与肥胖相关的FTO基因编码了一种依赖于2氧格酸的核酸脱甲基酶
Thomas Gerken1, Christophe A Girard, Yi-Chun Loraine Tung
1Chemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, 12 Mansfield Road, Oxford, Oxon OX1 3TA, UK.
概括
脂肪质量和与肥胖相关的 (FTO) 基因去甲基化DNA,可能将核酸甲基化与肥胖联系起来. 在 FTO FTO FTO.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- FTO基因中的遗传变异与增加的体重指数 (BMI) 有关.
- 与肥胖有关的FTO的精确分子功能仍然不清楚.
- FTO与Fe (II) -和2-oxoglutarate-dependent氧化酶具有相同的序列动机,这表明它具有潜在的酶活性.
研究的目的:
- 为了研究FTO基因的生物化学功能.
- 探索FTO在核酸修饰中的作用.
- 了解FTO在能量平衡调节中的生理相关性.
主要方法:
- 生物信息学分析以确定保存的序列动机.
- 使用重组小鼠Fto测试DNA脱甲基化活性的生物化学测试.
- 使用感染细胞进行细胞局部化研究.
- 在野生型小鼠中对Fto mRNA表达的定量分析.
主要成果:
- FTO表现出与Fe ((II) -和2-格酸盐依赖氧酶的序列相似性.
- 再组合Fto催化了单链DNA中3-甲基胺的脱甲基化.
- 反应产生了酸盐,甲和二氧化碳.
- Fto定位在细胞核中.
- 在大脑中,Fto mRNA的表达很高,特别是在参与能量平衡的下丘脑核中.
- 弧形核中的Fto mRNA水平是由食和禁食状态调节的.
结论:
- FTO作为Fe (II) -和2-氧格酸盐依赖的核酸脱甲基酶起作用.
- FTO在大脑中的核定位和表达模式表明它在调节能量平衡中起着作用.
- 需要进一步的研究来确定FTO的特定生理DNA基质,并阐明核酸甲基化与肥胖之间的联系.
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