DNA结合因子在遥远的调节区域塑造了小鼠甲基组
Michael B Stadler1, Rabih Murr, Lukas Burger
1Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Nature
|December 16, 2011
概括
结合DNA的因素会影响DNA甲基化模式,从而产生活跃的调节区域. 这项研究绘制了小鼠甲基组图,揭示了干细胞和神经元祖先中的细胞类型特异性模式.
科学领域:
- 表观遗传学和基因组学
- 哺乳动物基因组法规 哺乳动物基因组法规
背景情况:
- 细胞因子甲基化是哺乳动物的一个关键的表观遗传机制.
- 对于DNA甲基化模式的精确调节还没有完全理解.
研究的目的:
- 为了研究控制DNA甲基化模式的规则.
- 识别和描述受DNA甲基化影响的调节区域.
主要方法:
- 在干细胞和神经元祖先中生成基对分辨率小鼠甲基组.
- 定量分析以确定低甲基化区域 (LMR).
- 检测DNase I过敏,增强剂染色素标记和增强剂活性.
主要成果:
- 确定LMR (平均30%甲基化) 作为CpG贫乏的远程调节元素.
- 证明DNA结合因子占据了LMR,并且对于它们的形成是必要和足够的.
- 由细胞类型特定的转录因子驱动的细胞类型特定的LMR的确认.
结论:
- DNA结合因子对DNA甲基化产生局部控制.
- 这种机制可以识别活跃的监管区域.
- 为小鼠基因组提供了全面的甲基组参考.
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