Journal
ELIFE
Volume 6, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.27451
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Funding
- Biotechnology and Biological Sciences Research Council [BB/N006453/1]
- Biological Physical Sciences Institute [50093701]
- European Commission [289995]
- Royal Society [NF160208]
- Swedish Research Council
- Medical Research Council [MR/K01580X/1]
- BBSRC [BB/P000746/1, BB/N006453/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/N006453/1, BB/P000746/1] Funding Source: researchfish
- Medical Research Council [MR/K01580X/1] Funding Source: researchfish
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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.
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