Coordinated active repression operates via transcription factor cooperativity and multiple inactive promoter states in a developing organism
Refining transcriptional levels via active repression in a euchromatic context represents a critical regulatory process. While the molecular players of active repression are well described, their dynamics remain obscure. Here, we used snail expression dynamics as a paradigm to uncover how repression, mediated by the Snail (Sna) repressor, can be imposed within a developing tissue. Combining live imaging and mathematical modeling, we show that Sna-mediated repression is cooperative and that cooperativity is primarily mediated by the distal enhancer. Repression shifts transcription bursting dynamics from a two-state ON/OFF regime to a three-state repressed regime with two temporally distinct OFF states. Mutating Sna binding sites suggests that repression introduces the long-lasting inactive state, which is stabilized by cooperativity. Our approach offers quantitative insights into the dynamics of repression and how transcription factor cooperativity coordinates cell fate decisions within a tissue.
Authors
- Louise Maillard (ORCID: https://orcid.org/0009-0009-9346-1976)
- Virginia L Pimmett (ORCID: https://orcid.org/0000-0002-5786-7989)
- Mounia Lagha (ORCID: https://orcid.org/0000-0002-7082-1950)
- Maria Douaihy (ORCID: https://orcid.org/0009-0002-7258-7413)
- Ovidiu Radulescu (ORCID: https://orcid.org/0000-0001-6453-5707)
- Antonio Trullo (ORCID: https://orcid.org/0000-0001-7560-3859)
- Hélène Lenden Hasse (ORCID: https://orcid.org/0000-0001-9387-8784)
- Jérémy Dufourt (ORCID: https://orcid.org/0000-0003-4043-7250)
- Pablo Garcia Idieder
- Mélissa Costes (ORCID: https://orcid.org/0009-0001-6765-6245)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université de Montpellier (FR)
- Institut de Génétique Moléculaire de Montpellier (FR)
- Institut de Recherche en Infectiologie de Montpellier (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1038/s41467-025-62907-3
- Citations
- 1
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- European Molecular Biology Organization
- University of Chicago
- Agence Nationale de la Recherche
- Ligue Contre le Cancer
- Centre National de la Recherche Scientifique
- Fondation Bettencourt Schueller
- Université de Montpellier