Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins.

Autor: Wutz G; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria., Várnai C; Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, UK., Nagasaka K; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria., Cisneros DA; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria., Stocsits RR; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria., Tang W; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria., Schoenfelder S; Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, UK., Jessberger G; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria., Muhar M; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria., Hossain MJ; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Walther N; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Koch B; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Kueblbeck M; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Ellenberg J; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Zuber J; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria., Fraser P; Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, UK.; Department of Biological Science, Florida State University, Tallahassee, FL, USA., Peters JM; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria peters@imp.ac.at.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2017 Dec 15; Vol. 36 (24), pp. 3573-3599. Date of Electronic Publication: 2017 Dec 07.
DOI: 10.15252/embj.201798004
Abstrakt: Mammalian genomes are spatially organized into compartments, topologically associating domains (TADs), and loops to facilitate gene regulation and other chromosomal functions. How compartments, TADs, and loops are generated is unknown. It has been proposed that cohesin forms TADs and loops by extruding chromatin loops until it encounters CTCF, but direct evidence for this hypothesis is missing. Here, we show that cohesin suppresses compartments but is required for TADs and loops, that CTCF defines their boundaries, and that the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops. In the absence of WAPL and PDS5 proteins, cohesin forms extended loops, presumably by passing CTCF sites, accumulates in axial chromosomal positions (vermicelli), and condenses chromosomes. Unexpectedly, PDS5 proteins are also required for boundary function. These results show that cohesin has an essential genome-wide function in mediating long-range chromatin interactions and support the hypothesis that cohesin creates these by loop extrusion, until it is delayed by CTCF in a manner dependent on PDS5 proteins, or until it is released from DNA by WAPL.
(© 2017 The Authors.)
Databáze: MEDLINE
Externí odkaz: