title: Rapid movement and transcriptional re-localization of human cohesin on DNA.
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.
authors: Research Institute of Molecular Pathology (IMP), Vienna, Austria.
authors: Iain F
authors: IF
authors: Davidson
authors: Research Institute of Molecular Pathology (IMP), Vienna, Austria.
authors: Daniela
authors: D
authors: Goetz
authors: Research Institute of Molecular Pathology (IMP), Vienna, Austria.
authors: Maciej P
authors: MP
authors: Zaczek
authors: Research Institute of Molecular Pathology (IMP), Vienna, Austria.|Max F. Perutz Laboratories, University of Vienna, Vienna, Austria.
authors: Maxim I
authors: MI
authors: Molodtsov
authors: Research Institute of Molecular Pathology (IMP), Vienna, Austria.
authors: Pim J
authors: PJ
authors: Huis In 't Veld
authors: Research Institute of Molecular Pathology (IMP), Vienna, Austria.
authors: Florian
authors: F
authors: Weissmann
authors: Research Institute of Molecular Pathology (IMP), Vienna, Austria.
authors: Gabriele
authors: G
authors: Litos
authors: Research Institute of Molecular Pathology (IMP), Vienna, Austria.
authors: David A
authors: DA
authors: Cisneros
authors: The Francis Crick Institute, London, UK.
authors: Maria
authors: M
authors: Ocampo-Hafalla
authors: Research Institute of Molecular Pathology (IMP), Vienna, Austria.
authors: Rene
authors: R
authors: Ladurner
authors: The Francis Crick Institute, London, UK.
authors: Frank
authors: F
authors: Uhlmann
authors: Research Institute of Molecular Pathology (IMP), Vienna, Austria.|Max F. Perutz Laboratories, University of Vienna, Vienna, Austria.|The Rockefeller University, New York, NY, USA.
authors: Alipasha
authors: A
authors: Vaziri
authors: Research Institute of Molecular Pathology (IMP), Vienna, Austria peters@imp.ac.at.
authors: Jan-Michael
authors: 0000-0003-2820-3195
authors: JM
authors: Peters
mesh_terms: D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D006801:Humans; D012097:Repressor Proteins / Q000378:metabolism; D000072760:Single Molecule Imaging; D013997:Time Factors; D014158:Transcription, Genetic; D000097722:Cohesins
chemical_list: D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004247:DNA; D012097:Repressor Proteins; D000097722:Cohesins; C000619697:CTCF protein, human
keywords: cell cycle; cohesin; genome organization; single‐molecule TIRF microscopy; transcription