DNA甲基化和转录因子之间的竞争决定了NRF1的结合
Silvia Domcke1,2, Anaïs Flore Bardet1, Paul Adrian Ginno1
1Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH 4058 Basel, Switzerland.
Nature
|December 18, 2015
概括
基因甲基化限制了转录因子 (TF) 的结合,特别是NRF1. TF结合可以促进低甲基化,从而进一步促进TF占用和基因调节.
科学领域:
- 表观遗传学和基因调控
- 分子生物学
- 基因组学
背景情况:
- 细胞转录因子 (TFs) 控制基因活性,但只结合它们的DNA基因子集.
- 染色体结构可以限制TF可访问性,但染色体状态在指导TF结合中的作用尚不清楚.
- DNA甲基化是影响基因组功能的关键表观遗传标记.
研究的目的:
- 研究DNA甲基化对受限转录因子结合的作用.
- 了解染色体状态,特别是DNA甲基化如何指导干细胞中的TF结合.
主要方法:
- 在DNA甲基化和不甲基化条件下,在小鼠干细胞中绘制DNase-I过敏部位.
- 在受限甲基化位点中分析TF基因丰富.
- 评估对DNA甲基化变化和TF相互作用的NRF1结合动态.
主要成果:
- 对于含有CpG的TF基因,特别是NRF1的基因,限制甲基化的部位是富含的.
- 转录因子NRF1在未甲基化基因组中结合了数千个额外的位点,从而增加了转录.
- 恢复DNA甲基转移酶活动导致再甲基化,超过NRF1结合.
- 移除邻近的基因或TFs会导致局部超甲基化和NRF1结合的丧失,这表明TF通过DNA甲基化具有合作性.
结论:
- 基因甲基化作为TF结合的障碍,特别是对于NRF1等对甲基化敏感的TF.
- 对DNA甲基化敏感TF的结合可能需要额外的决定因素来诱导局部低甲基化.
- 一些因素的甲基化去除使其他因素占用,解释调节区域低甲基化的合作原则.
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