Capicua is a fast-acting transcriptional brake.

TitleCapicua is a fast-acting transcriptional brake.
Publication TypeJournal Article
Year of Publication2021
AuthorsPatel, AL, Zhang, L, Keenan, SE, Rushlow, CA, Fradin, C, Shvartsman, SY
JournalCurr Biol
Volume31
Issue16
Pagination3639-3647.e5
Date Published2021 08 23
ISSN1879-0445
KeywordsAnimals, Drosophila, Drosophila Proteins, Gene Expression Regulation, Developmental, HMGB Proteins, Humans, Repressor Proteins
Abstract

<p>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. 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. 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.</p>

DOI10.1016/j.cub.2021.05.061
Alternate JournalCurr Biol
PubMed ID34166605
PubMed Central IDPMC8612007
Grant ListDP2 EB024247 / EB / NIBIB NIH HHS / United States
R01 GM063024 / GM / NIGMS NIH HHS / United States
R01 HD085870 / HD / NICHD NIH HHS / United States
F32 GM119297 / GM / NIGMS NIH HHS / United States
R01 GM086537 / GM / NIGMS NIH HHS / United States