转基因RNAi揭示了CTCF在H19基因印记中的基本功能
Andrew M Fedoriw1, Paula Stein, Petr Svoboda
1Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Science (New York, N.Y.)
|January 13, 2004
概括
CCCTC结合因子 (CTCF) 蛋白质在卵细胞生长过程中保护H19差异甲基化域 (DMD) 免受甲基化. 卵细胞中CTCF缺乏会影响其发育和H19 DMD甲基化.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 发展生物学 发展生物学
- 基因组学就是基因组学.
背景情况:
- 印制基因调节,特别是H19和胰岛素样生长因子2 (IGF2),依赖于CCCCTC结合因子 (CTCF) 与差异甲基化域 (DMD) 相互作用.
- 在 oogenesis 期间维持 H19 DMD 的低甲基化状态的机制以及 CTCF 在这个过程中的作用仍然不清楚.
研究的目的:
- 调查CTCF在 oogenesis 期间维持 H19 不同甲基化域 (DMD) 的低甲基化状态中的作用.
- 确定CTCF缺乏对卵细胞甲基化和发育能力的影响.
主要方法:
- 利用转基因RNA干扰 (RNAi) 方法创建具有降低CTCF蛋白水平的卵细胞.
- 评估了H19 DMD的甲基化状态,并评估了CTCF缺陷卵细胞的发育能力.
主要成果:
- 减少CTCF蛋白的卵细胞显示H19 DMD的甲基化增加.
- 缺乏CTCF的卵细胞显示发育能力下降,表明植入前发育受损.
- 在卵细胞生长过程中,CTCF似乎对H19 DMD的de novo甲基化起着保护作用.
结论:
- 在卵细胞发育过程中,CTCF对于保护H19差异甲基化域 (DMD) 免受de novo甲基化至关重要.
- 对于正常的植入前发育,CTCF是必需的,这凸显了它在早期胚胎形成中的关键作用.
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