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Transcription factor clusters regulate genes in eukaryotic cells

Artikel i vetenskaplig tidskrift
Författare A. J. M. Wollman
Sviatlana Shashkova
E. G. Hedlund
Rosmarie Friemann
Stefan Hohmann
M. C. Leake
Publicerad i Elife
Volym 6
ISSN 2050-084X
Publiceringsår 2017
Publicerad vid Institutionen för kemi och molekylärbiologi
Språk English
Länkar doi.org/10.7554/eLife.27451
Ämnesord intrinsically disordered proteins, yeast saccharomyces-cerevisiae, mig1, glucose repressor, single-molecule level, dna-binding proteins, in-vivo, fluorescent protein, facilitated diffusion, intersegment transfer, mammalian-cells, Life Sciences & Biomedicine - Other Topics
Ämneskategorier Kemi, Biologiska vetenskaper

Sammanfattning

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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