凝聚素通过转录,CTCF和Wapl定位在哺乳动物基因组中
Georg A Busslinger1, Roman R Stocsits1, Petra van der Lelij1
1Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Campus-Vienna-Biocenter 1, A-1030 Vienna, Austria.
Nature
|April 21, 2017
概括
哺乳动物的基因组组织依赖于CCCTC结合因子 (CTCF) 和凝聚素. 这项研究揭示了转录可以转移凝聚素,影响其在CTCF位点的定位和基因调节.
科学领域:
- 基因组学
- 分子生物学
- 表观遗传学
背景情况:
- 哺乳动物的基因组由CTCF和凝聚素组织成染色体循环和拓相关的域.
- CTCF结合点对于凝聚素介导的长距离染色体相互作用至关重要,但凝聚素的招募机制尚不清楚.
研究的目的:
- 研究哺乳动物基因组中的凝聚蛋白分布因素.
- 阐明转录,CTCF和Wapl在凝聚力学和局部化中的作用.
主要方法:
- 使用CTCF枯竭的小鼠纤维细胞观察凝聚性行为.
- 在没有CTCF和Wapl的情况下分析了凝聚蛋白的分布.
- 研究了改变基因表达对凝聚素局部化的影响.
主要成果:
- 凝聚素未能在缺乏CTCF的细胞中进入CTCF位点,而是聚集在活跃的基因转录起点.
- 在没有CTCF和Wapl的情况下,凝聚蛋白在活跃基因的3'-端形成"岛屿",受基因表达水平的影响.
- 在长距离的DNA中观察到转录介导的凝聚素转位,类似于酵母.
结论:
- 转录在哺乳动物凝聚力转移中起着关键作用,有助于其在CTCF位点的定位.
- 活性基因可以通过转录介导转位或Wapl介导释放从凝聚素释放,影响基因调节.
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