Optogenetic dissection of transcriptional repression in a multicellular organism

Jiaxi Zhao, Nicholas C. Lammers, Simon Alamos, Yang Joon Kim, Gabriella Martini and Hernan G. Garcia ()
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Jiaxi Zhao: University of California
Nicholas C. Lammers: University of California
Simon Alamos: University of California
Yang Joon Kim: University of California
Gabriella Martini: University of California
Hernan G. Garcia: University of California

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-53539-0

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