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Dynamic and Selective Low-Complexity Domain Interactions Revealed by Live-Cell Single-Molecule Imaging

Shasha Chong, Claire Dugast-Darzacq, Zhe Liu, Peng Dong, Gina M. Dailey, Claudia Cattoglio, Sambashiva Banala, Luke Lavis, Xavier Darzacq, Robert Tjian
doi: https://doi.org/10.1101/208710
Shasha Chong
1Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
2Howard Hughes Medical Institute, University of California, Berkeley, CA, USA.
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Claire Dugast-Darzacq
1Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
4CIRM Center of Excellence, University of California, Berkeley, CA, USA.
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Zhe Liu
3Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
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Peng Dong
3Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
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Gina M. Dailey
1Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
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Claudia Cattoglio
1Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
2Howard Hughes Medical Institute, University of California, Berkeley, CA, USA.
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Sambashiva Banala
3Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
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Luke Lavis
3Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
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Xavier Darzacq
1Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
4CIRM Center of Excellence, University of California, Berkeley, CA, USA.
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Robert Tjian
1Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
2Howard Hughes Medical Institute, University of California, Berkeley, CA, USA.
4CIRM Center of Excellence, University of California, Berkeley, CA, USA.
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  • For correspondence: jmlim@berkeley.edu
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Abstract

Many eukaryotic transcription factors (TFs) contain intrinsically disordered low-complexity domains (LCDs) but how they perform transactivation functions remains unclear. Recent studies report that TF-LCDs can undergo hydrogel formation or liquid-liquid phase separation in vitro. Here, live-cell single-molecule imaging reveals that TF-LCDs form local high concentration interaction hubs at synthetic and endogenous genomic loci. TF-LCD hubs stabilize DNA binding, recruit RNA polymerase II (Pol II) and activate transcription. LCD-LCD interactions within hubs are highly dynamic, display selectivity with binding partners, and are differentially sensitive to disruption by hexanediols. These findings suggest that under physiological conditions, rapid reversible and multivalent LCD-LCD interactions occur between TFs and the Pol II machinery, which underpins a central mechanism for transactivation and plays a key role in gene expression and disease.

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Posted May 16, 2018.
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Dynamic and Selective Low-Complexity Domain Interactions Revealed by Live-Cell Single-Molecule Imaging
Shasha Chong, Claire Dugast-Darzacq, Zhe Liu, Peng Dong, Gina M. Dailey, Claudia Cattoglio, Sambashiva Banala, Luke Lavis, Xavier Darzacq, Robert Tjian
bioRxiv 208710; doi: https://doi.org/10.1101/208710
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Dynamic and Selective Low-Complexity Domain Interactions Revealed by Live-Cell Single-Molecule Imaging
Shasha Chong, Claire Dugast-Darzacq, Zhe Liu, Peng Dong, Gina M. Dailey, Claudia Cattoglio, Sambashiva Banala, Luke Lavis, Xavier Darzacq, Robert Tjian
bioRxiv 208710; doi: https://doi.org/10.1101/208710

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