Coordinated active repression operates via transcription factor cooperativity and multiple inactive promoter states in a developing organism

Virginia L. Pimmett, Maria Douaihy, Louise Maillard, Antonio Trullo, Pablo Garcia Idieder, Mélissa Costes, Jeremy Dufourt, Hélène Lenden-Hasse, Ovidiu Radulescu () and Mounia Lagha ()
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Virginia L. Pimmett: CNRS UMR 5535
Maria Douaihy: CNRS UMR 5535
Louise Maillard: CNRS UMR 5535
Antonio Trullo: CNRS UMR 5535
Pablo Garcia Idieder: CNRS UMR 5535
Mélissa Costes: CNRS UMR 5535
Jeremy Dufourt: CNRS UMR 5535
Hélène Lenden-Hasse: CNRS UMR 5535
Ovidiu Radulescu: INSERM
Mounia Lagha: CNRS UMR 5535

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract 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.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62907-3

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DOI: 10.1038/s41467-025-62907-3

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