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EMBO J. 2016 Dec 15;35(24):2671-2685. Epub 2016 Oct 31.

Rapid movement and transcriptional re-localization of human cohesin on DNA.

Author information

1
Research Institute of Molecular Pathology (IMP), Vienna, Austria.
2
Max F. Perutz Laboratories, University of Vienna, Vienna, Austria.
3
The Francis Crick Institute, London, UK.
4
The Rockefeller University, New York, NY, USA.
5
Research Institute of Molecular Pathology (IMP), Vienna, Austria peters@imp.ac.at.

Abstract

The spatial organization, correct expression, repair, and segregation of eukaryotic genomes depend on cohesin, ring-shaped protein complexes that are thought to function by entrapping DNA It has been proposed that cohesin is recruited to specific genomic locations from distal loading sites by an unknown mechanism, which depends on transcription, and it has been speculated that cohesin movements along DNA could create three-dimensional genomic organization by loop extrusion. However, whether cohesin can translocate along DNA is unknown. Here, we used single-molecule imaging to show that cohesin can diffuse rapidly on DNA in a manner consistent with topological entrapment and can pass over some DNA-bound proteins and nucleosomes but is constrained in its movement by transcription and DNA-bound CCCTC-binding factor (CTCF). These results indicate that cohesin can be positioned in the genome by moving along DNA, that transcription can provide directionality to these movements, that CTCF functions as a boundary element for moving cohesin, and they are consistent with the hypothesis that cohesin spatially organizes the genome via loop extrusion.

KEYWORDS:

cell cycle; cohesin; genome organization; single‐molecule TIRF microscopy; transcription

PMID:
27799150
PMCID:
PMC5167347
DOI:
10.15252/embj.201695402
[Indexed for MEDLINE]
Free PMC Article

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