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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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Published in: | Nature communications 2024-10, Vol.15 (1), p.9263-11, Article 9263 |
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description | 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. |
doi_str_mv | 10.1038/s41467-024-53539-0 |
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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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>39461978</pmid><doi>10.1038/s41467-024-53539-0</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-4434-8351</orcidid><orcidid>https://orcid.org/0000-0002-5212-3649</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | 631/136 631/1647/2253 631/553 631/57 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 |
title | Optogenetic dissection of transcriptional repression in a multicellular organism |
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