一个依赖CTCF的边界控制的甲基化控制了Igf2基因的印记表达
1Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0540, USA.
Nature
|June 6, 2000
概括
基因组印记调节了基因表达. 一个依赖CTCF的绝缘体通过阻断增强剂活性来控制印制基因表达,而DNA甲基化将其功能限制在特定的等位基因上.
科学领域:
- 遗传学 是一个遗传学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 胰岛素样生长因子2 (Igf2) 和H19基因表达受到基因印记的调节.
- 这些基因共享一种增强剂,但H19在母体表达,Igf2在父体表达.
- 在H19上游的父特异性甲基化对于印记至关重要.
研究的目的:
- 为了研究H19.19的上游甲基化区域的功能.
- 确定CTCF在监管增强器活动和印记方面的作用.
- 阐明DNA甲基化控制印制基因表达的机制.
主要方法:
- 甲基化区域的删除分析.
- 在体外研究中,CTCF与甲基化CpG结合.
- 在体内评估增强剂阻断活性.
主要成果:
- 甲基化区域含有依赖于CTCF的增强剂阻断元素.
- 对CTCF结合点的甲基化阻止了CTCF的结合.
- 删除CTCF部位取消了增强剂阻断活性,导致基因表达的改变.
- 由于DNA甲基化模式,这种绝缘体的活性是异位基因特异性的.
结论:
- 一个依赖于CTCF的增强器阻断元件作为控制Igf2印记的绝缘体起作用.
- 通过调节增强剂边界,DNA甲基化调节增强剂-促进剂接入.
- 这种机制突显了DNA甲基化如何控制印制基因中的基因表达.
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