biostudies-literatureKeenan SENICHD NIH HHSNational Institutes of Health794-801.e4https://www.ebi.ac.uk/biostudies/studies/S-EPMC7161736biostudies-literatureUnknown52(6)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 analysDevelopmental cellRapid Dynamics of Signal-Dependent Transcriptional Repression by Capicua.PMC7161736R01 HD085870Shvartsman SYDjabrayan NJBlythe SAKeenan SEMarmion RAWieschaus EFfalseRapid Dynamics of Signal-Dependent Transcriptional Repression by Capicua.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 analys2020-01-01T00:00:00Z2020 Mar2026-05-01T17:33:59.063Z2025-02-19T03:41:40.74ZS-EPMC71617363214263110.1016/j.devcel.2020.02.004