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Lookup NU author(s): Dr Adam WollmanORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© Wollman et al.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.
Author(s): Wollman AJM, Shashkova S, Hedlund EG, Friemann R, Hohmann S, Leake MC
Publication type: Article
Publication status: Published
Online publication date: 25/08/2017
Acceptance date: 24/08/2017
Date deposited: 10/02/2020
ISSN (electronic): 2050-084X
Publisher: eLife Sciences Publications Ltd
PubMed id: 28841133
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