The architecture of binding cooperativity between densely bound transcription factors

Offir Lupo, Divya Krishna Kumar, Rotem Livne, Michal Chappleboim, Idan Levy, Naama Barkai

Research output: Contribution to journalArticlepeer-review


The binding of transcription factors (TFs) along genomes is restricted to a subset of sites containing their preferred motifs. TF-binding specificity is often attributed to the co-binding of interacting TFs; however, apart from specific examples, this model remains untested. Here, we define dependencies among budding yeast TFs that localize to overlapping promoters by profiling the genome-wide consequences of co-depleting multiple TFs. We describe unidirectional interactions, revealing Msn2 as a central factor allowing TF binding at its target promoters. By contrast, no case of mutual cooperation was observed. Particularly, Msn2 retained binding at its preferred promoters upon co-depletion of fourteen similarly bound TFs. Overall, the consequences of TF co-depletions were moderate, limited to a subset of promoters, and failed to explain the role of regions outside the DNA-binding domain in directing TF-binding preferences. Our results call for re-evaluating the role of cooperative interactions in directing TF-binding preferences.

Original languageEnglish
Pages (from-to)732-745.e5
Number of pages14
JournalCell Systems
Issue number9
Early online date31 Jul 2023
StatePublished - 20 Sep 2023

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology


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