University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology
Publication Date
2020-12-20
Document Type
Article Preprint
Disciplines
Amino Acids, Peptides, and Proteins | Cell Biology | Molecular Biology | Structural Biology | Systems Biology
Abstract
DNA loop extrusion by condensins and decatenation by DNA topoisomerase II (topo II) drive mitotic chromosome compaction and individualization. Here, we reveal that the linker histone H1.8 regulates chromatin levels of condensins and topo II. In vitro chromatin reconstitution experiments demonstrate that H1.8 inhibits binding of condensins and topo II to nucleosome arrays. Accordingly, H1.8 depletion in Xenopus egg extracts increased condensins and topo II levels on mitotic chromatin. Chromosome morphology and Hi-C analyses suggest that H1.8 depletion makes chromosomes thinner and longer likely through shortening the average loop size and reducing DNA amount in each layer of mitotic loops. Furthermore, H1.8-mediated suppression of condensins and topo II binding to chromatin limits chromosome individualization by preventing resolution of interchromosomal linkages. While linker histones locally compact DNA by clustering nucleosomes, we propose that H1.8 controls chromosome morphology and topological organization through restricting the loading of condensins and topo II on chromatin.
Keywords
Cell Biology, histones, DNA topoisomerase II, chromatin, condensins, chromosomes
Rights and Permissions
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
10.1101/2020.12.20.423657
Source
bioRxiv 2020.12.20.423657; doi: https://doi.org/10.1101/2020.12.20.423657. Link to preprint on bioRxiv.
Journal/Book/Conference Title
bioRxiv
Repository Citation
Choppakatla P, Dekker B, Cutts EE, Vannini A, Dekker J, Funabiki H. (2020). Linker histone H1.8 inhibits chromatin-binding of condensins and DNA topoisomerase II to tune chromosome compaction and individualization [preprint]. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/2020.12.20.423657. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1871
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, Cell Biology Commons, Molecular Biology Commons, Structural Biology Commons, Systems Biology Commons
Comments
This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.