Transcription factors (TFs) that bind common DNA motifs in vitro occupy distinct sets of promoters in vivo, raising the question of how binding specificity is achieved. TFs are enriched with intrinsically disordered regions (IDRs). Such regions commonly form promiscuous interactions, yet their unique properties might also benefit specific binding-site selection. We examine this using Msn2 and Yap1, TFs of distinct families that contain long IDRs outside their DNA-binding domains. We find that these IDRs are both necessary and sufficient for localizing to the majority of target promoters. This IDR-directed binding does not depend on any localized domain but results from a multitude of weak determinants distributed throughout the entire IDR sequence. Furthermore, IDR specificity is conserved between distant orthologs, suggesting direct interaction with multiple promoters. We propose that distribution of sensing determinants along extended IDRs accelerates binding-site detection by rapidly localizing TFs to broad DNA regions surrounding these sites.

转录因子（TF），其结合共同DNA基序在体外占据不同组启动子的体内，提出了如何实现结合特异性的问题。TF富含内在无序区（IDR）。这样的区域通常形成混杂的相互作用，但是它们的独特性质也可能有益于特定的结合位点选择。我们使用不同的家族的Msn2和Yap1来检查这一点，这些家族的DNA结合域之外包含长IDR。我们发现这些IDRs对于定位到大多数目标启动子都是必要和充分的。这种IDR定向结合不依赖于任何局部域，而是由分布在整个IDR序列中的众多弱决定簇引起的。此外，IDR特异性在遥远的直系同源物之间是保守的，表明与多个启动子的直接相互作用。