Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology
Amino Acids, Peptides, and Proteins | Cell Biology | Molecular Biology | Structural Biology | Systems Biology
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.
Cell Biology, histones, DNA topoisomerase II, chromatin, condensins, chromosomes
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DOI of Published Version
bioRxiv 2020.12.20.423657; doi: https://doi.org/10.1101/2020.12.20.423657. Link to preprint on bioRxiv.
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
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