在哺乳动物调节进化过程中,对转作用电路的保护
Andrew B Stergachis1, Shane Neph1, Richard Sandstrom1
1Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
Nature
|November 21, 2014
概括
哺乳动物的基因调节主要是通过跨调节电路的变化而演变,而不是 cis 调节元素. 这允许监管可塑性,同时保持基本的蜂网络架构.
科学领域:
- 基因组学就是基因组学.
- 进化生物学 进化生物学
- 分子生物学分子生物学
背景情况:
- 哺乳动物进化表明身体计划得到保护,但基因组约束有限.
- 了解监管演变需要区分 cis 和 trans 作用因素.
研究的目的:
- 量化对哺乳动物调节演变的 cis 与 trans 作用的贡献.
- 为了比较鼠标和人类之间的转录因子结合景观.
主要方法:
- 基因组DNase I足迹在25种小鼠细胞/组织类型中.
- 识别了860万个核酸分辨率转录因子占用地点.
- 对老鼠和人类转录因子足迹和监管网络的比较分析.
主要成果:
- 鼠标和人类转录因子足迹在它们的监管词汇中共享约95%的相似性.
- 只有大约20%的老鼠转录因子足迹有人类的ortologues,表明cis-regulatory周转.
- 尽管存在 cis-landscape 变化,但约有 50% 的双向调节相互作用通过进化创新得到保护.
- 转录因子连接的细胞网络架构在老鼠和人类之间高度保留.
结论:
- 哺乳动物基因调节的进化选择针对的是跨调节电路.
- 这种定位使得Cis-regulatory可塑性成为可能,同时保持核心网络功能.
- 通过转录因子识别序列的适应性演变来维持保存的调节网络.
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