embj.201695402.pdf (2.18 MB)
Rapid movement and transcriptional re-localization of human cohesin on DNA
journal contributionposted on 2020-07-17, 16:28 authored by Iain F Davidson, Daniela Goetz, Maciej P Zaczek, Maxim I Molodtsov, Pim J Huis in 't Veld, Florian Weissmann, Gabriele Litos, David A Cisneros, Maria Ocampo-Hafalla, Rene Ladurner, Frank Uhlmann, Alipasha Vaziri, Jan-Michael Peters
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.
cell cyclecohesingenome organizationsingle‐molecule TIRF microscopytranscriptionCCCTC-Binding FactorCell Cycle ProteinsChromosomal Proteins, Non-HistoneDNAHumansRepressor ProteinsSingle Molecule ImagingTime FactorsTranscription, GeneticUhlmann FC001198Molodtsov FC00175006 Biological Sciences08 Information and Computing Sciences11 Medical and Health SciencesDevelopmental Biology