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Updated: Nov 1, 2025

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Capicua is a fast-acting transcriptional brake
Aleena L Patel1, Lili Zhang2, Shannon E Keenan1
1Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08540, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08540, USA.
Abstract:
Even though transcriptional repressors are studied with ever-increasing molecular resolution, the temporal aspects of gene repression remain poorly understood. Here, we address the dynamics of transcriptional repression by Capicua (Cic), which is essential for normal development and is commonly mutated in human cancers and neurodegenerative diseases.1,2 We report the speed limit for Cic-dependent gene repression based on live imaging and optogenetic perturbations in the early Drosophila embryo, where Cic was originally discovered.3 Our measurements of Cic concentration and intranuclear mobility, along with real-time monitoring of the activity of Cic target genes, reveal remarkably fast transcriptional repression within minutes of removing an optogenetic de-repressive signal. In parallel, quantitative analyses of transcriptional bursting of Cic target genes support a repression mechanism providing a fast-acting brake on burst generation. This work sets quantitative constraints on potential mechanisms for gene regulation by Cic.
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