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2h ago

Genome-Wide Molecular Timer Controls Developmental Stages in C. elegans

The MYRF-1/LIN-42 feedback circuit enforces once‑per‑stage transcriptional pulses that couple gene-expression waves to developmental checkpoints.

The MYRF-1 and LIN-42 feedback circuit functions as a non-repeating genomic master clock, operating as a one-way molecular ratchet to drive sequential pulses of developmental gene expression. Credit: Neuroscience News
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Overview

  • Researchers identified a reciprocal feedback loop between the transcription factor MYRF-1 and the PERIOD-like repressor LIN-42 that acts as a genome-wide master developmental clock in C. elegans.
  • MYRF-1 triggers each stage-specific pulse of gene expression and is required to license the checkpoint that lets the worm progress to the next developmental stage.
  • Once activated by MYRF-1, newly made LIN-42 binds to MYRF-1 and shortens its nuclear residence to limit the amplitude and duration of each transcriptional pulse.
  • The team used classical genetics, DNA and protein sequencing, and AlphaFold structural predictions, and published the findings in PNAS (Wu et al., 2026; DOI: 10.1073/pnas.2606846123).
  • Follow-up experiments are mapping the proteins' physical interactions and how independent cellular clocks stay phase-locked across tissues, work that could inform studies of developmental disorders though clinical links remain unproven.