由Dnmt1基因中的母性效应突变中断的基因组印记
C Y Howell1, T H Bestor, F Ding
1Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Cell
|April 6, 2001
概括
在早期哺乳动物胚胎中,DNA甲基转移酶-1卵细胞变体 (Dnmt1o) 对于维持早期哺乳动物胚胎印记基因位置的甲基化模式至关重要. 它的缺失导致发育缺陷和失去了等位基因特异性表达.
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:
- 基因组甲基化模式对于哺乳动物发育至关重要.
- DNA甲基转移酶-1 (Dnmt1) 在体细胞中维持这些模式.
- 鼠标卵细胞和早期胚胎使用Dnmt1变体Dnmt1o,而不是Dnmt1.
研究的目的:
- 研究Dnmt1o在维持甲基化模式和支持胚胎发育中的作用.
- 为了确定Dnmt1o在印记位置的特定功能.
主要方法:
- 删除Dnmt1基因的卵细胞特异性促进子和第一个外因子,以消除Dnmt1o.
- 从淘汰小鼠的卵细胞和胚胎中分析甲基化模式和基因表达.
- 对同卵性雌性异卵性后代的胚胎死亡率的评估.
主要成果:
- 同卵性Dnmt1o缺乏的动物是可行的,但来自同卵性母亲的异卵性胎儿在妊娠晚期表现出高死亡率.
- 在Dnmt1o缺乏的卵细胞中,甲基化模式正常确立.
- 缺少Dnmt1o的胚胎在某些印记位置表现出异位基因特异性表达和甲基化损失.
- 在8细胞阶段胚胎中,Dnmt1o暂时局限于核.
结论:
- 在早期胚胎发生过程中,Dnmt1o对于维持甲基化和在印记位置的等位基特表达至关重要.
- Dnmt1o可能在第四个胚胎S阶段提供关键维护甲基转移酶活性.
- 缺少Dnmt1o会导致发育失败,这凸显了它在基因组印记维护中的重要性.
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