促进体内和局部染色体特征决定LAD中的基因抑制
Christ Leemans1, Marloes C H van der Zwalm1, Laura Brueckner1
1Division of Gene Regulation and Oncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Cell
|April 16, 2019
概括
拉米纳相关域 (LAD) 创建一个抑制色素环境,使基因沉默. 一些促进体可以逃脱这种抑制,其活性取决于促进体序列和LAD中的局部染色体特征.
科学领域:
- 表观遗传学
- 基因组学
- 染色体生物学
背景情况:
- 膜相关域 (LAD) 是核外围的异色素区域.
- 在基因沉默中LADs的作用是有争议的:它们是否积极抑制基因或是基因不活性的结果.
研究的目的:
- 调查LAD是否对嵌入基因施加压制性染色质环境.
- 确定决定基因从LAD中介抑制中逃脱的因素.
主要方法:
- 基因组工程重新定位人类促进器进入和退出LAD.
- 记者基因测试以测量促进体活性和转录延长.
- 在数千个基因组位置系统地插入记者.
主要成果:
- 数以百计的人类促进体在从LAD转移到中性基因组位置时变得活跃.
- 一组LAD嵌入式促进体 ("逃生体") 显示部分活性,转录延长减弱.
- 逃生促进体活性与内在促进体序列特性和LAD中的局部染色体变异有关,而不仅仅是促进体强度.
结论:
- 可以使基因沉默.
- 来自LAD的基因逃逸受到促进物序列和局部染色体环境的复杂相互作用的影响.
- 这项研究为理解抑制性染色体域内的基因调节提供了框架.
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