ePrints

Transcription factor clusters regulate genes in eukaryotic cells

Lookup NU author(s): Dr Adam WollmanORCiD

Downloads

• Published version [.pdf]

Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 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.

Publication metadata

Author(s): Wollman AJM, Shashkova S, Hedlund EG, Friemann R, Hohmann S, Leake MC

Publication type: Article

Publication status: Published

Journal: eLife

Year: 2017

Volume: 6

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

URL: https://doi.org/10.7554/eLife.27451

DOI: 10.7554/eLife.27451

PubMed id: 28841133

Altmetrics

Funding

Share