Optogenetic dissection of transcriptional repression in a multicellular organism

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...

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Bibliographic Details
Published in:Nature communications 2024-10, Vol.15 (1), p.9263-11, Article 9263
Main Authors: Zhao, Jiaxi, Lammers, Nicholas C., Alamos, Simon, Kim, Yang Joon, Martini, Gabriella, Garcia, Hernan G.
Format: Article
Language:English
Subjects:
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Animals
Biology
Dissection
Embryos
Gene expression
Gene Expression Regulation
Gene loci
Gene regulation
Gene silencing
Genetics
Humanities and Social Sciences
In vivo methods and tests
Information processing
Mathematical models
multidisciplinary
Optics
Optogenetics
Proteins
Repressor Proteins - genetics
Repressor Proteins - metabolism
Science
Science (multidisciplinary)
Single-Cell Analysis
Transcription factors
Transcription Factors - genetics
Transcription Factors - metabolism
Transcription, Genetic
Zinc finger proteins
Zinc Fingers
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Summary: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. Using optogenetics in the fly embryo, this study investigates how a transcriptional repressor drives switch-like, rapidly reversible repression by modulating transcriptional burst frequency, offering insights into gene regulation dynamics in development.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-53539-0