Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology
Biochemistry, Biophysics, and Structural Biology | Cell and Developmental Biology
DNA loop extrusion by condensins and decatenation by DNA topoisomerase II (topo II) are thought to drive mitotic chromosome compaction and individualization. Here, we reveal that the linker histone H1.8 antagonizes condensins and topo II to shape mitotic chromosome organization. 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 through shortening the average loop size and reducing the DNA amount in each layer of mitotic loops. Furthermore, excess loading of condensins and topo II to chromosomes by H1.8 depletion causes hyper-chromosome individualization and dispersion. We propose that condensins and topo II are essential for chromosome individualization, but their functions are tuned by the linker histone to keep chromosomes together until anaphase.
Hi-C, chromatin, chromosome compaction, chromosomes, gene expression, linker histone, mitosis, nucleosome, xenopus
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Copyright © 2021, Choppakatla et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
DOI of Published Version
Choppakatla P, Dekker B, Cutts EE, Vannini A, Dekker J, Funabiki H. Linker histone H1.8 inhibits chromatin binding of condensins and DNA topoisomerase II to tune chromosome length and individualization. Elife. 2021 Aug 18;10:e68918. doi: 10.7554/eLife.68918. PMID: 34406118; PMCID: PMC8416026. Link to article on publisher's site
Choppakatla P, Dekker B, Cutts EE, Vannini A, Dekker J, Funabiki H. (2021). Linker histone H1.8 inhibits chromatin binding of condensins and DNA topoisomerase II to tune chromosome length and individualization. Open Access Publications by UMass Chan Authors. https://doi.org/10.7554/eLife.68918. Retrieved from https://escholarship.umassmed.edu/oapubs/4884
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