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<p>Genetic oscillators drive precisely timed gene expression, crucial for development and physiology. Using the <i>C. elegans</i> molting clock as a model, we investigate how oscillators can schedule the orderly expression of thousands of genes. Single-cell RNA sequencing reveals a broad peak phase dispersion in individual tissues, mirrored by rhythmic changes in chromatin accessibility at thousands of regulatory elements identified by time-resolved ATAC-seq. We develop a linear model to predict chromatin dynamics based on the binding of &gt;200 transcription factors. This identifies nine key regulators acting additively to determine the peak phase and amplitude of each regulatory element. Strikingly, these factors can also generate constitutive, non-rhythmic activity through destructive interference. Validating its power, the model accurately predicts the impact of GRH-1/Grainyhead perturbation on both chromatin and transcript dynamics. This work provides a conceptual framework for understanding how combinatorial, non-cooperative transcription factor binding schedules complex gene expression patterns in development and other dynamic biological processes.</p>

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A scheduler for rhythmic gene expression

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月10日

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  • Dimos Gaidatzis,
  • Maike Graf-Landua,
  • Stephen P Methot,
  • Michaela Wölk,
  • Giovanna Brancati,
  • Yannick P Hauser,
  • Milou W M Meeuse,
  • Smita Nahar,
  • Kathrin Braun,
  • Marit van der Does,
  • Sirisha Aluri,
  • Hubertus Kohler,
  • Sebastien Smallwood,
  • Helge Großhans

摘要

Genetic oscillators drive precisely timed gene expression, crucial for development and physiology. Using the C. elegans molting clock as a model, we investigate how oscillators can schedule the orderly expression of thousands of genes. Single-cell RNA sequencing reveals a broad peak phase dispersion in individual tissues, mirrored by rhythmic changes in chromatin accessibility at thousands of regulatory elements identified by time-resolved ATAC-seq. We develop a linear model to predict chromatin dynamics based on the binding of >200 transcription factors. This identifies nine key regulators acting additively to determine the peak phase and amplitude of each regulatory element. Strikingly, these factors can also generate constitutive, non-rhythmic activity through destructive interference. Validating its power, the model accurately predicts the impact of GRH-1/Grainyhead perturbation on both chromatin and transcript dynamics. This work provides a conceptual framework for understanding how combinatorial, non-cooperative transcription factor binding schedules complex gene expression patterns in development and other dynamic biological processes.