促进体DNA的短暂循环甲基化
Sara Kangaspeska1, Brenda Stride, Raphaël Métivier
1European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
Nature
|March 7, 2008
概括
动态DNA甲基化和脱甲基化循环发生在人类基因促进体中,影响基因表达. 这一循环过程与雌激素受体α和RNA聚合酶II等关键蛋白质的活性有关.
科学领域:
- 表观遗传学和基因调控
- 分子生物学分子生物学
- 人类细胞过程
背景情况:
- CpG二核酸甲基化通常会沉默转录,并在细胞分裂过程中保持.
- 富含CpG的区域 (CpG岛屿) 通常在活跃的基因起始点发现,但通常是低甲基的.
- 之前的研究表明,在对脱乙酶抑制剂的反应中,DNA甲基化发生了动态变化.
研究的目的:
- 研究人类基因促进体中的循环甲基化和脱甲基化模式.
- 确定DNA甲基化循环,基因转录和蛋白质占用之间的关系.
- 探索可以重新启动静止基因中的甲基化循环的条件.
主要方法:
- 在5个选定的人类基因促进体中分析DNA甲基化动态,包括对雌激素 (E2) 敏感的三叶草因子1 (TFF1/pS2) 基因.
- 监测循环甲基化和脱甲基化,周期约为100分钟.
- 在活跃转录过程中,将DNA甲基化模式与雌激素受体α (ERalpha) 和RNA聚合酶II (polII) 的周期性占用相关联.
主要成果:
- 循环甲基化和脱甲基化CpG二核酸是选择的人类基因促进体的特征.
- 对于pS2基因来说,在活跃转录期间,DNA甲基化发生在ERalpha和polII循环结合之后.
- 特定条件可以在静止细胞系中诱导甲基化循环,其中含有甲基化PS2促进体,与ERalpha和PS2再表达相关.
结论:
- 基因甲基化不是静态的,但可以在活跃的人类基因促进体中发生动态循环变化.
- 这种甲基化循环与转录机制密切相关,包括ERalpha和polII.
- 诱导甲基化循环可能会重新激活被沉默的基因,为表观遗传控制机制提供了洞察力.
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