Rapid Dynamics of Signal-Dependent Transcriptional Repression by Capicua.

TitleRapid Dynamics of Signal-Dependent Transcriptional Repression by Capicua.
Publication TypeJournal Article
Year of Publication2020
AuthorsKeenan, SE, Blythe, SA, Marmion, RA, Djabrayan, NJ-V, Wieschaus, EF, Shvartsman, SY
JournalDev Cell
Date Published2020 Mar 23
KeywordsActive Transport, Cell Nucleus, Animals, Cell Nucleus, Drosophila melanogaster, Drosophila Proteins, Extracellular Signal-Regulated MAP Kinases, Gene Expression Regulation, Developmental, HMGB Proteins, MAP Kinase Signaling System, Protein Binding, Repressor Proteins

<p>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.</p>

Alternate JournalDev Cell
PubMed ID32142631
PubMed Central IDPMC7161736
Grant ListR01 HD085870 / HD / NICHD NIH HHS / United States