Capicua is a fast-acting transcriptional brake

Aleena L. Patel, Lili Zhang, Shannon E. Keenan, Christine A. Rushlow, Cécile Fradin, Stanislav Y. Shvartsman

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3639-3647.e5
JournalCurrent Biology
Volume31
Issue number16
DOIs
StatePublished - Aug 23 2021

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Keywords

  • Capicua
  • Drosophila
  • ERK signaling
  • bursting
  • photoswitchable MEK
  • repressor
  • transcription

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