Transcription factor clusters regulate genes in eukaryotic cells
- University of York, United Kingdom
- University of Gothenburg, Sweden
Abstract
Transcription is regulated through binding factors to gene promoters to activate or repress expression, however, the mechanisms by which factors find targets remain unclear. Using single-molecule fluorescence microscopy, we determined in vivo stoichiometry and spatiotemporal dynamics of a GFP tagged repressor, Mig1, from a paradigm signaling pathway of Saccharomyces cerevisiae. We find the repressor operates in clusters, which upon extracellular signal detection, translocate from the cytoplasm, bind to nuclear targets and turnover. Simulations of Mig1 configuration within a 3D yeast genome model combined with a promoter-specific, fluorescent translation reporter confirmed clusters are the functional unit of gene regulation. In vitro and structural analysis on reconstituted Mig1 suggests that clusters are stabilized by depletion forces between intrinsically disordered sequences. We observed similar clusters of a co-regulatory activator from a different pathway, supporting a generalized cluster model for transcription factors that reduces promoter search times through intersegment transfer while stabilizing gene expression.
Article and author information
Author details
Sviatlana Shashkova
Funding
Biotechnology and Biological Sciences Research Council (grant BB/N006453/1)
- Adam JM Wollman
- Mark C Leake
Medical Research Council (MR/K01580X/1)
- Mark C Leake
European Commission (289995)
- Sviatlana Shashkova
- Erik G Hedlund
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Wollman et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 7,614
- views
-
- 1,144
- downloads
-
- 88
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Citations by DOI
-
- 88
- citations for umbrella DOI https://doi.org/10.7554/eLife.27451
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Transcription factor clusters regulate genes in eukaryotic cells
eLife 6:e27451.
https://doi.org/10.7554/eLife.27451
