Evidence for DNA-mediated nuclear compartmentalization distinct from phase separation

eLife

Hervé Marie-Nelly¹  Claire Dugast-Darzacq¹  Anders S Hansen¹  Alec Basil Heckert²  Kayla K Umemoto³  Robert Tjian³  Sheila S Teves³  David Trombley McSwiggen³  Xavier Darzacq³  Yvonne Hao³ 

[1] California Institute of Regenerative Medicine Center of Excellence, University of California, Berkeley, Berkeley, United States;Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada;Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States;

关键词: transcription factors;    phase separation;    nuclear organization;    single particle tracking;    RNA Polymerase II;    chromatin function;   

DOI  :  10.7554/eLife.47098

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown