Linker histone H1.8 inhibits chromatin binding of condensins and DNA topoisomerase II to tune chromosome length and individualization
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 r...
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eLife Sciences Publications Ltd
2021
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oai:doaj.org-article:e53d35ae1e1748bb8cdf3a62b3e3e7a32021-11-26T07:06:35ZLinker histone H1.8 inhibits chromatin binding of condensins and DNA topoisomerase II to tune chromosome length and individualization10.7554/eLife.689182050-084Xe68918https://doaj.org/article/e53d35ae1e1748bb8cdf3a62b3e3e7a32021-08-01T00:00:00Zhttps://elifesciences.org/articles/68918https://doaj.org/toc/2050-084XDNA 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.Pavan ChoppakatlaBastiaan DekkerErin E CuttsAlessandro VanniniJob DekkerHironori FunabikieLife Sciences Publications Ltdarticlechromosome compactionmitosislinker histonenucleosomeHi-CchromatinMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
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chromosome compaction mitosis linker histone nucleosome Hi-C chromatin Medicine R Science Q Biology (General) QH301-705.5 |
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chromosome compaction mitosis linker histone nucleosome Hi-C chromatin Medicine R Science Q Biology (General) QH301-705.5 Pavan Choppakatla Bastiaan Dekker Erin E Cutts Alessandro Vannini Job Dekker Hironori Funabiki Linker histone H1.8 inhibits chromatin binding of condensins and DNA topoisomerase II to tune chromosome length and individualization |
description |
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. |
format |
article |
author |
Pavan Choppakatla Bastiaan Dekker Erin E Cutts Alessandro Vannini Job Dekker Hironori Funabiki |
author_facet |
Pavan Choppakatla Bastiaan Dekker Erin E Cutts Alessandro Vannini Job Dekker Hironori Funabiki |
author_sort |
Pavan Choppakatla |
title |
Linker histone H1.8 inhibits chromatin binding of condensins and DNA topoisomerase II to tune chromosome length and individualization |
title_short |
Linker histone H1.8 inhibits chromatin binding of condensins and DNA topoisomerase II to tune chromosome length and individualization |
title_full |
Linker histone H1.8 inhibits chromatin binding of condensins and DNA topoisomerase II to tune chromosome length and individualization |
title_fullStr |
Linker histone H1.8 inhibits chromatin binding of condensins and DNA topoisomerase II to tune chromosome length and individualization |
title_full_unstemmed |
Linker histone H1.8 inhibits chromatin binding of condensins and DNA topoisomerase II to tune chromosome length and individualization |
title_sort |
linker histone h1.8 inhibits chromatin binding of condensins and dna topoisomerase ii to tune chromosome length and individualization |
publisher |
eLife Sciences Publications Ltd |
publishDate |
2021 |
url |
https://doaj.org/article/e53d35ae1e1748bb8cdf3a62b3e3e7a3 |
work_keys_str_mv |
AT pavanchoppakatla linkerhistoneh18inhibitschromatinbindingofcondensinsanddnatopoisomeraseiitotunechromosomelengthandindividualization AT bastiaandekker linkerhistoneh18inhibitschromatinbindingofcondensinsanddnatopoisomeraseiitotunechromosomelengthandindividualization AT erinecutts linkerhistoneh18inhibitschromatinbindingofcondensinsanddnatopoisomeraseiitotunechromosomelengthandindividualization AT alessandrovannini linkerhistoneh18inhibitschromatinbindingofcondensinsanddnatopoisomeraseiitotunechromosomelengthandindividualization AT jobdekker linkerhistoneh18inhibitschromatinbindingofcondensinsanddnatopoisomeraseiitotunechromosomelengthandindividualization AT hironorifunabiki linkerhistoneh18inhibitschromatinbindingofcondensinsanddnatopoisomeraseiitotunechromosomelengthandindividualization |
_version_ |
1718409750701408256 |