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Updated: Dec 26, 2025

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Rapid Dynamics of Signal-Dependent Transcriptional Repression by Capicua
Shannon E Keenan1, Shelby A Blythe2, Robert A Marmion3
1Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08540, USA; The Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08540, USA.
Abstract:
Optogenetic perturbations, live imaging, and time-resolved ChIP-seq assays in Drosophila embryos were used to dissect the ERK-dependent control of the HMG-box repressor Capicua (Cic), which plays critical roles in development and is deregulated in human spinocerebellar ataxia and cancers. We established that Cic target genes are activated before significant downregulation of nuclear localization of Cic and demonstrated that their activation is preceded by fast dissociation of Cic from the regulatory DNA. We discovered that both Cic-DNA binding and repression are rapidly reinstated in the absence of ERK activation, revealing that inductive signaling must be sufficiently sustained to ensure robust transcriptional response. Our work provides a quantitative framework for the mechanistic analysis of dynamics and control of transcriptional repression in development.
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