在小鼠生殖系中的表观遗传重编程期间的染色质动力学
Petra Hajkova1, Katia Ancelin1, Tanja Waldmann2
1Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.
Nature
|March 21, 2008
概括
小鼠原始生殖细胞 (PGCs) 经历DNA脱甲基化和印记擦除. 这项研究揭示了两阶段的染色质变化,包括质子替代,与PGC重编程期间的DNA脱甲基化有关.
科学领域:
- 发育生物学 发展生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 胚胎细胞系的发展涉及到全能生成.
- 基因脱甲基化和父母印记抹去是小鼠原始生殖细胞 (PGCs) 胚胎日11.5.5左右的关键事件.
- 基于PGC重编程的机制在很大程度上是未知的.
研究的目的:
- 为了研究与DNA脱甲基化和印记擦除相关的染色质变化,在小鼠的PGC中.
- 了解驱动PGC重编程的分子机制.
主要方法:
- 在不同发育阶段 (E8.5和生殖腺) 的PGC中分析染色质修饰和基因组变异.
- 检查基因素陪伴子积累的情况 (HIRA和NAP-1).
- 染色质变化的相关性与全基因组DNA脱甲基化.
主要成果:
- PGC染色体重编程发生在两个不同的步骤中,从E8.5.5.的多能性类似的签名开始.
- 主要的核架构变化,基因组修饰删除和基因组变异交换发生在PGC进入生殖腺时.
- 基因组辅导体HIRA和NAP-1在经历重编程的PGC中积累,这表明在基因组替代中发挥了作用.
- 染色质变化与全基因组DNA脱甲基化密切相关.
结论:
- 在PGC重编程过程中观察到的染色质重排序中,基因组替代可能是关键的.
- 时机表明,基因组替代可能是对DNA脱甲基化的反应,可能是通过基于DNA修复的机制,而不是先决条件.
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