GHT-SELEX表现出意想不到的高内在序列特异性和许多人类转录因子的复杂DNA结合
Arttu Jolma1, Aldo Hernandez-Corchado2,3, Ally W H Yang1
1Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
bioRxiv : the preprint server for biology
|November 28, 2024
概括
许多人类转录因子 (TF) 显示出比预期的更高的DNA序列特异性,挑战了以前的假设. 这种内在的特异性使得TF能够在大型人类基因组中准确地识别其目标基因.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 生物信息学是一种生物信息学.
背景情况:
- 人类调节基因组学面临的挑战是由于短,退化的转录因子 (TF) DNA结合动机和庞大的基因组,导致错误的阳性结合部位预测.
- 传统的方法往往低估了TFs的内在序列特异性.
研究的目的:
- 调查广泛的人类TFs的实际序列特异性.
- 为了将体外确定的结合位与体内基因组结合区域进行比较.
- 探索TFs中的DNA结合域 (DBD) 模块化.
主要方法:
- 基因组HT-SELEX (高通量SELEX) 被采用,涉及超过1500个循环体外选择实验,用于25个家庭的179个TF,使用碎片化,裸体DNA.
- 通过GHT-SELEX识别的TF结合部位与体内ChIP-seq数据进行了比较.
- 进行了TF动机扫描和DNA结合域参与策略的分析.
主要成果:
- 许多人类TF表现出比先前预期的要高得多的序列特异性.
- 由GHT-SELEX识别的基因组结合区域在体内与ChIP-seq峰值非常相似.
- TF图案扫描性能高度依赖于图案导出和扫描方法.
- 长C2H2指蛋白显示模块化DNA识别,利用不同的DBDs子集绑定多种点.
结论:
- 与传统观点相反,TF通常具有足够的内在特异性,可以独立地划分它们的细胞目标.
- 这些发现完善了我们对TF-DNA相互作用和调控基因组学的理解.
- 模块化DNA被TFs识别是一种常见的进化策略.
关键词:
在C2H2的基础上.C2H2 指 C2H2 指这就是ChIP-Seq.代码书 是一个代码书.具有DNA结合的特异性在GHT-SELEX中.基因调节 基因调节在HT-SELEXEX中使用.马吉克 (MAGIXIX) 是一个神奇的世界.模块化结合方式在PWM中使用PWM.位置重量矩阵的位置重量矩阵.这就是RCADEEMEM.这就是SELEXEX.在TFTFTFTFTFTFTFTFTFTFTFTF转录因子是一种转录因子.转录因子的结合部位更多相关视频
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