Abstract
RNA Polymerase II (Pol II) and transcription factors form concentrated hubs in cells via multivalent protein-protein interactions, often mediated by proteins with intrinsically disordered regions. During Herpes Simplex Virus infection, viral replication compartments (RCs) efficiently enrich host Pol II into membraneless domains, reminiscent of liquid-liquid phase-separation. Despite sharing several properties with phase-separated condensates, we show that RCs operate via a distinct mechanism wherein unrestricted nonspecific protein-DNA interactions efficiently outcompete host chromatin, profoundly influencing the way DNA binding proteins explore RCs. We find that the viral genome remains largely nucleosome-free, and this increase in accessibility allows Pol II and other DNA-binding proteins to repeatedly visit nearby DNA binding sites. This anisotropic behavior creates local accumulations of protein factors despite their unrestricted diffusion across RC boundaries. Our results reveal underappreciated consequences of nonspecific DNA binding in shaping gene activity, and suggest additional roles for chromatin in modulating nuclear function and organization.
Article and author information
Author details
Funding
National Institutes of Health (UO1- 497 EB021236)
- David Trombley McSwiggen
- Anders S Hansen
- Yvonne Hao
- Alec Basil Heckert
- Kayla K Umemoto
- Claire Dugast-Darzacq
- Xavier Darzacq
National Institutes of Health (U54-DK107980)
- David Trombley McSwiggen
- Anders S Hansen
- Yvonne Hao
- Alec Basil Heckert
- Kayla K Umemoto
- Claire Dugast-Darzacq
- Xavier Darzacq
California Institute for Regenerative Medicine (LA1-08013)
- Anders S Hansen
- Alec Basil Heckert
- Xavier Darzacq
Howard Hughes Medical Institute (003061)
- David Trombley McSwiggen
- Anders S Hansen
- Sheila S Teves
- Yvonne Hao
- Alec Basil Heckert
- Kayla K Umemoto
- Robert Tjian
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jessica K Tyler, Weill Cornell Medicine, United States
Publication history
- Received: March 26, 2019
- Accepted: April 29, 2019
- Accepted Manuscript published: April 30, 2019 (version 1)
- Accepted Manuscript updated: May 7, 2019 (version 2)
- Version of Record published: May 16, 2019 (version 3)
Copyright
© 2019, McSwiggen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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