Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
School of Science, Constructor University, 28759 Bremen, Germany.
Nucleic Acids Res. 2024 Aug 27;52(15):8763-8777. doi: 10.1093/nar/gkae521.
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.
无规则区域 (IDR) 引导转录因子 (TF) 到其基因组结合位点，这就提出了一个问题，即缺乏结构的区域如何编码复杂的结合模式。我们使用 TF Gln3 对此进行了研究，揭示了一组嵌入 IDR 的决定因素，这些决定因素指导 Gln3 结合到相应的功能相关启动子组，并能够在环境条件、磷酸模拟突变和同源物之间调整结合偏好。通过靶向突变，我们定义了短线性基序 (SLiM) 和共同结合 TF (Hap2) 在稳定呼吸链启动子上的 Gln3 中的作用，同时提供的证据表明，氮相关启动子上的 Gln3 结合由 IDR 氨基酸组成编码，与 SLiM 或共同结合 TF 无关。因此，尽管它们表面上很简单，但 TF IDR 可以通过 SLiM 介导和组成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。
