凝聚素在功能上与哺乳动物染色体臂上的CTCF有关
Vania Parelho1, Suzana Hadjur, Mikhail Spivakov
1Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK.
Cell
|February 2, 2008
概括
哺乳动物的凝聚蛋白在特定位置与DNA结合,由CTCF蛋白引导. 这种结合解释了凝聚素在基因调节中的作用,并将DNA序列与表观遗传信息结合起来.
科学领域:
- 分子生物学分子生物学
- 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.
背景情况:
- 凝聚素对于姐妹染色体凝聚力至关重要,对于精确的染色体分离和DNA修复至关重要.
- 凝聚素还影响基因表达和增强剂-促进剂相互作用,但机制尚不清楚.
- 缺乏了解哺乳动物中的凝聚素结合部位和相互作用体.
研究的目的:
- 为了确定哺乳动物染色体上的凝聚素结合部位.
- 为了阐明metazoans中的cohesins的功能相互作用者.
- 为了解释cohesins在基因调节中的非正规功能.
主要方法:
- 染色质分析用于绘制哺乳动物染色体上的凝聚性分布图.
- 在凝聚结位点识别序列图案.
- 研究CTCF在使用基因枯竭的凝聚性局部化中的作用.
主要成果:
- 哺乳动物染色体上的凝聚蛋白分布独立于转录活性.
- 哺乳动物的凝聚蛋白优先结合含有CTCF图案的DNase I过敏位点.
- 对于将凝聚物定位到这些地点,CTCF是必不可少的.
- 凝聚蛋白的定位受到通过CTCF的DNA序列和表观遗传状态的影响.
结论:
- 在哺乳动物中,CTCF作为招募cohesins到特定基因组位置的主要因素.
- 这次CTCF介导的招募为凝聚素在基因调节中的作用提供了机制性的解释.
- 凝聚蛋白定位将DNA序列信息与诸如DNA甲基化之类的表观遗传修饰整合在一起.
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