报告员CRISPR屏幕在Xist位点破译了cis-regulatory和trans-regulatory原则
Till Schwämmle1, Gemma Noviello1, Eleni Kanata1,2
1Systems Epigenetics, Otto Warburg Laboratories, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Nature structural & molecular biology
|October 6, 2025
概括
研究人员确定了控制X-染色体失活的Xist基因表达的关键转录因子 (TF). 这项研究揭示了近端和远端调节元素如何整合TF信号来控制基因激活和输出.
科学领域:
- 遗传学 遗传学 是一个
- 发展生物学 发展生物学
- 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:
- 发育基因依赖于 cis 调节元件 (RE) 和跨作用转录因子 (TF) 进行控制.
- 将TF输入集成到 cis 调节的环境中,是基因调节的一个重大挑战.
研究的目的:
- 为了全面识别调节小鼠Xist位点的TFs,并绘制它们与RE的相互作用.
- 阐明 Xist 基因调节的机制,这对于 X 染色体不活化至关重要.
主要方法:
- 开发了一种结合的CRISPR查方法.
- 使用内源性RNA和RE记者进行读取.
- 将该方法应用于小鼠Xist位点.
主要成果:
- 确定了一组暂时上调的TFs (例如,ZIC3) 调节二进制Xist激活的近接RE.
- 发现了以后起作用的发育TFs (例如,OTX2),针对高XistRNA水平的远端RE.
- OCT4被确定为近端和远端元素的强有力的激活剂.
结论:
- 靠近的RE向因子调解二进制基因的开关决策.
- 远程RE准因素控制着转录输出的大小.
- 这为开发基因调节提供了一个模型,整合了TF-RE相互作用.
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