德洛索菲拉胚胎中的染色质可访问性是由转录因子开创和增强器激活决定的
Kaelan J Brennan1, Melanie Weilert1, Sabrina Krueger1
1Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
Developmental cell
|August 9, 2023
概括
像Zelda这样的先驱转录因子 (TFs) 建立了最初的染色质可访问性,而TFs的模式增强了基因激活. 这种两层模型解释了增强剂在开发过程中如何变得可访问和活跃.
科学领域:
- 发展生物学 发展生物学
- 基因组学就是基因组学.
- 计算生物学 计算生物学
背景情况:
- 染色质可访问性对于转录因子 (TFs) 结合cis调节DNA至关重要.
- 区分那些推动可访问性的TF与那些不推动的TF仍然具有挑战性.
- 深度学习为分析监管DNA中的复杂序列规则提供了新的方法.
研究的目的:
- 剖析不同TFs在调节染色质可访问性的作用.
- 了解开拓者和模式TFs之间的等级关系.
- 用Drosophila开发来建模增强可访问性和激活的过程.
主要方法:
- 对高分辨率TF结合和染色质可访问性数据的分析.
- 应用可解释的深度学习模型来识别序列规则.
- 基因验证实验用于确认计算预测.
主要成果:
- 确定了先驱TF Zelda和轴模式TFs之间的等级关系.
- 泽尔达先驱色素的可访问性与其动图亲和关系成比例.
- 图案TF增加了特定序列环境中的染色质可访问性,以激活增强剂.
结论:
- 染色体可访问性有两个层次:开拓性和激活性.
- 像Zelda这样的TF的先驱使增强器可以访问,但不一定是活跃的.
- 增强器激活需要TFs的正确组合,导致可访问性的第二层.
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