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Nucleic Acids Res. 2017 Nov 2;45(19):11159-11173. doi: 10.1093/nar/gkx741.

Enrichment of dynamic chromosomal crosslinks drive phase separation of the nucleolus.

Author information

1
Department of Mathematics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
2
Department of Mathematics, University of South Carolina, Columbia, SC 29808, USA.
3
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
4
Curriculum of Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
5
Department of Applied Physical Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Abstract

Regions of highly repetitive DNA, such as those found in the nucleolus, show a self-organization that is marked by spatial segregation and frequent self-interaction. The mechanisms that underlie the sequestration of these sub-domains are largely unknown. Using a stochastic, bead-spring representation of chromatin in budding yeast, we find enrichment of protein-mediated, dynamic chromosomal cross-links recapitulates the segregation, morphology and self-interaction of the nucleolus. Rates and enrichment of dynamic crosslinking have profound consequences on domain morphology. Our model demonstrates the nucleolus is phase separated from other chromatin in the nucleus and predicts that multiple rDNA loci will form a single nucleolus independent of their location within the genome. Fluorescent labeling of budding yeast nucleoli with CDC14-GFP revealed that a split rDNA locus indeed forms a single nucleolus. We propose that nuclear sub-domains, such as the nucleolus, result from phase separations within the nucleus, which are driven by the enrichment of protein-mediated, dynamic chromosomal crosslinks.

PMID:
28977453
PMCID:
PMC5737219
DOI:
10.1093/nar/gkx741
[Indexed for MEDLINE]
Free PMC Article

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