University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology; Graduate School of Biomedical Sciences
Publication Date
2019-06-21
Document Type
Article Preprint
Disciplines
Amino Acids, Peptides, and Proteins | Bioinformatics | Computational Biology | Genetic Phenomena | Genomics | Molecular Biology | Structural Biology
Abstract
Chromosome folding is extensively modulated as cells progress through the cell cycle. During mitosis, condensin complexes fold chromosomes in helically arranged nested loop arrays. In interphase, the cohesin complex generates loops that can be stalled at CTCF sites leading to positioned loops and topologically associating domains (TADs), while a separate process of compartmentalization drives the spatial segregation of active and inactive chromatin domains. We used synchronized cell cultures to determine how the mitotic chromosome conformation is transformed into the interphase state. Using Hi-C, chromatin binding assays, and immunofluorescence we show that by telophase condensin-mediated loops are lost and a transient folding intermediate devoid of most loops forms. By late telophase, cohesin-mediated CTCF-CTCF loops and positions of TADs start to emerge rapidly. Compartment boundaries are also established in telophase, but long-range compartmentalization is a slow process and proceeds for several hours after cells enter G1. Our results reveal the kinetics and order of events by which the interphase chromosome state is formed and identify telophase as a critical transition between condensin and cohesin driven chromosome folding.
Keywords
genomics, chromosome folding, condensin-to-cohesin transition, telophase, interphase
Rights and Permissions
The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
10.1101/678474
Source
bioRxiv 678474; doi: https://doi.org/10.1101/678474. Link to preprint on bioRxiv service.
Journal/Book/Conference Title
bioRxiv
Repository Citation
Abramo, Kristin; Valton, Anne-Laure; Venev, Sergey V.; Ozadam, Hakan; Fox, A. Nicole; and Dekker, Job, "A chromosome folding intermediate at the condensin-to-cohesin transition during telophase" (2019). University of Massachusetts Medical School Faculty Publications. 1614.
https://escholarship.umassmed.edu/faculty_pubs/1614
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Amino Acids, Peptides, and Proteins Commons, Bioinformatics Commons, Computational Biology Commons, Genetic Phenomena Commons, Genomics Commons, Molecular Biology Commons, Structural Biology Commons