Intrinsically disordered regions (IDRs) guide transcription factors (TFs) to their genomic binding sites, raising the question of how structure-lacking regions encode for complex binding patterns. We investigated this using the TF Gln3, revealing sets of IDR-embedded determinants that direct Gln3 binding to respective groups of functionally related promoters, and enable tuning binding preferences between environmental conditions, phospho-mimicking mutations, and orthologs. Through targeted mutations, we defined the role of short linear motifs (SLiMs) and co-binding TFs (Hap2) in stabilizing Gln3 at respiration-chain promoters, while providing evidence that Gln3 binding at nitrogen-associated promoters is encoded by the IDR amino-acid composition, independent of SLiMs or co-binding TFs. Therefore, despite their apparent simplicity, TF IDRs can direct and regulate complex genomic binding patterns through a combination of SLiM-mediated and composition-encoded interactions.

中文翻译：

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转录因子的无序序列通过整合不同的序列语法和相互作用类型来调节基因组结合


本质无序区域 (IDR) 引导转录因子 (TF) 到达其基因组结合位点，从而提出了结构缺乏区域如何编码复杂结合模式的问题。我们使用 TF Gln3 对此进行了研究，揭示了一组 IDR 嵌入的决定簇，这些决定簇指导 Gln3 与相应的功能相关启动子组结合，并能够调整环境条件、磷酸模拟突变和直向同源物之间的结合偏好。通过靶向突变，我们定义了短线性基序 (SLiM) 和共结合 TF (Hap2) 在稳定呼吸链启动子上的 Gln3 中的作用，同时提供证据表明氮相关启动子上的 Gln3 结合是由 IDR 氨基编码的酸组成，独立于 SLiM 或共结合 TF。因此，尽管它们表面上很简单，但 TF IDR 可以通过 SLiM 介导和成分编码相互作用的组合来指导和调节复杂的基因组结合模式。