Title | Capicua is a fast-acting transcriptional brake. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Patel, AL, Zhang, L, Keenan, SE, Rushlow, CA, Fradin, C, Shvartsman, SY |
Journal | Curr Biol |
Volume | 31 |
Issue | 16 |
Pagination | 3639-3647.e5 |
Date Published | 2021 Aug 23 |
ISSN | 1879-0445 |
Keywords | Animals, 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> |
DOI | 10.1016/j.cub.2021.05.061 |
Alternate Journal | Curr Biol |
PubMed ID | 34166605 |
PubMed Central ID | PMC8612007 |
Grant List | DP2 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 |