Msn2转录因子的内在无序区域使用交织的序列语法编码多个功能
Vladimir Mindel1, Sagie Brodsky1, Aileen Cohen1
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Nucleic acids research
|December 18, 2023
概括
转录因子 (TF) 中的内在无序区域 (IDR) 使用不同的序列代码来进行DNA结合和基因激活. 这项研究揭示了Msn2的IDR如何将这些代码整合到精确的促进者选择和协同激活器招募中.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 生物化学 生物化学
背景情况:
- 内在无序区域 (IDR) 在真核蛋白中很普遍,但它们的序列功能关系尚未完全理解.
- 转录因子 (TFs) 使用IDR来调节基因表达,通过指导促进体选择和招募协同激活体.
- 芽酵母TF Msn2可以作为一个模型来研究IDR如何编码这些双重功能.
研究的目的:
- 阐明转录因子 (TF) 的内在无序区域 (IDR) 如何编码促进体结合特异性和协同激活体招募.
- 调查 Msn2 IDR 序列变异及其在基因组结合,联合激活剂招募和基因诱导中的功能之间的关系.
主要方法:
- 对大量设计的 Msn2 IDR 突变物进行生成和分析.
- 基因组结合特异性的比较,协同激活剂招募试验,以及突变物种之间的基因诱导水平.
- 生物信息分析用于识别管理不同功能的基于序列的代码.
主要成果:
- 无论是DNA结合特异性还是转录活性都受到Msn2 IDR (>600氨基酸) 内的多个区域的影响.
- 破坏转录活动的突变通常对Msn2结合特异性没有影响.
- 基于组合的密码用于结合特异性,而基于严格的基因密码用于协同激活剂招募和转录,因而归因于不同的敏感性.
结论:
- Msn2 TF在其IDR中使用交织的序列语法来编码不同的功能.
- 一个放松的,基于构成的代码控制着绑定特异性,而一个严格的,基于动机的代码控制着转录.
- 这表明一个潜在的可概括的IDR设计范式,用于编码多个蛋白质功能.
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