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Optogenetic dissection of transcriptional repression in a multicellular organism

Affiliations
  • 1Department of Physics, University of California, Berkeley, CA, USA.
  • 2Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • 3Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA.
  • 4Biophysics Graduate Group, University of California, Berkeley, CA, USA.
  • 5Department of Genome Sciences, University of Washington, Seattle, WA, USA.
  • 6Department of Plant and Microbial Biology, University of California, Berkeley, CA, USA.
  • 7Feedstocks Division, Joint BioEnergy Institute, Emeryville, CA, USA.
  • 8Environmental Genomics and Systems Biology Division, LBNL, Berkeley, CA, USA.
  • 9Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
  • 10Department of Physics, University of California, Berkeley, CA, USA. hggarcia@berkeley.edu.
  • 11Biophysics Graduate Group, University of California, Berkeley, CA, USA. hggarcia@berkeley.edu.
  • 12Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA. hggarcia@berkeley.edu.
  • 13Institute for Quantitative Biosciences-QB3, University of California, Berkeley, CA, USA. hggarcia@berkeley.edu.
  • 14Chan Zuckerberg Biohub, San Francisco, CA, USA. hggarcia@berkeley.edu.

Published on:

October 27, 2024

Abstract

Transcriptional control is fundamental to cellular function. However, despite knowing that transcription factors can repress or activate specific genes, how these functions are implemented at the molecular level has remained elusive, particularly in the endogenous context of developing animals. Here, we combine optogenetics, single-cell live-imaging, and mathematical modeling to study how a zinc-finger repressor, Knirps, induces switch-like transitions into long-lived quiescent states. Using optogenetics, we demonstrate that repression is rapidly reversible (~1 min) and memoryless. Furthermore, we show that the repressor acts by decreasing the frequency of transcriptional bursts in a manner consistent with an equilibrium binding model. Our results provide a quantitative framework for dissecting the in vivo biochemistry of eukaryotic transcriptional regulation.