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Pico-C Maps Show Embryo DNA Forms 3D Scaffold Before Genes Turn On

Researchers identify sequence cues plus pioneer factors as drivers of this early architecture.

Overview

  • Using the low-input Pico-C method, scientists generated high-resolution chromatin maps in fruit fly embryos as early as nuclear cycle 9, revealing loops and domains assembled prior to zygotic genome activation.
  • The work shows genome organization precedes transcription, indicating 3D folding helps program which genes will activate during development.
  • Artificial intelligence models support that DNA sequence encodes instructions for its own three-dimensional configuration.
  • Depleting pioneer factors disrupted early chromatin organization, underscoring their role in establishing pre-activation structure.
  • A companion study in human cells found that removing chromatin tethers collapsed genome architecture and triggered a misread viral-like immune response.