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<p>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 <i>snail</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月1日

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  • Virginia L. Pimmett,
  • Maria Douaihy,
  • Louise Maillard,
  • Antonio Trullo,
  • Pablo Garcia Idieder,
  • Mélissa Costes,
  • Jeremy Dufourt,
  • Hélène Lenden-Hasse,
  • Ovidiu Radulescu,
  • Mounia Lagha

摘要

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.