Intrinsically disordered regions facilitate target search to drive promoter selectivity by a yeast transcription factor.

ABSTRACT: Transcription factors regulate gene expression by binding specific DNA motifs, yet only a fraction of putative sites is occupied in vivo. Intrinsically disordered regions have emerged as key contributors to promoter selectivity, but the underlying mechanisms remain incompletely understood. Here, we use single-molecule optical tweezers to dissect how disordered regions influence DNA binding by Msn2, a yeast stress-response regulator. We show that these regions power a search mechanism, facilitating initial non-specific association with DNA and promoting one-dimensional scanning toward target motifs, supported by charge-mediated interactions. Remarkably, this mechanism displays sequence sensitivity, with promoter-derived sequences enhancing both initial binding and scanning rates, demonstrat

SUBMITTER: Strugo N 

PROVIDER: S-EPMC12804832 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature