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

Author

Listed:
  • Virginia L. Pimmett

    (CNRS UMR 5535)

  • Maria Douaihy

    (CNRS UMR 5535
    INSERM)

  • 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
    University of Montpellier)

  • Hélène Lenden-Hasse

    (CNRS UMR 5535)

  • Ovidiu Radulescu

    (INSERM)

  • Mounia Lagha

    (CNRS UMR 5535)

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.

Suggested Citation

  • Virginia L. Pimmett & Maria Douaihy & Louise Maillard & Antonio Trullo & Pablo Garcia Idieder & Mélissa Costes & Jeremy Dufourt & Hélène Lenden-Hasse & Ovidiu Radulescu & Mounia Lagha, 2025. "Coordinated active repression operates via transcription factor cooperativity and multiple inactive promoter states in a developing organism," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62907-3
    DOI: 10.1038/s41467-025-62907-3
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    References listed on IDEAS

    as
    1. Maëlle Bellec & Jérémy Dufourt & George Hunt & Hélène Lenden-Hasse & Antonio Trullo & Amal Zine El Aabidine & Marie Lamarque & Marissa M. Gaskill & Heloïse Faure-Gautron & Mattias Mannervik & Melissa , 2022. "The control of transcriptional memory by stable mitotic bookmarking," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Virginia L. Pimmett & Matthieu Dejean & Carola Fernandez & Antonio Trullo & Edouard Bertrand & Ovidiu Radulescu & Mounia Lagha, 2021. "Quantitative imaging of transcription in living Drosophila embryos reveals the impact of core promoter motifs on promoter state dynamics," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    3. Jiaxi Zhao & Nicholas C. Lammers & Simon Alamos & Yang Joon Kim & Gabriella Martini & Hernan G. Garcia, 2024. "Optogenetic dissection of transcriptional repression in a multicellular organism," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    4. Katjana Tantale & Encar Garcia-Oliver & Marie-Cécile Robert & Adèle L’Hostis & Yueyuxiao Yang & Nikolay Tsanov & Rachel Topno & Thierry Gostan & Alja Kozulic-Pirher & Meenakshi Basu-Shrivastava & Kama, 2021. "Stochastic pausing at latent HIV-1 promoters generates transcriptional bursting," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    5. Jeremy Dufourt & Antonio Trullo & Jennifer Hunter & Carola Fernandez & Jorge Lazaro & Matthieu Dejean & Lucas Morales & Saida Nait-Amer & Katharine N. Schulz & Melissa M. Harrison & Cyril Favard & Ovi, 2018. "Temporal control of gene expression by the pioneer factor Zelda through transient interactions in hubs," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
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