TY - JOUR TI - Linker histone H1.8 inhibits chromatin binding of condensins and DNA topoisomerase II to tune chromosome length and individualization AU - Choppakatla, Pavan AU - Dekker, Bastiaan AU - Cutts, Erin E AU - Vannini, Alessandro AU - Dekker, Job AU - Funabiki, Hironori A2 - Marston, Adèle L A2 - Tyler, Jessica K A2 - Marston, Adèle L VL - 10 PY - 2021 DA - 2021/08/18 SP - e68918 C1 - eLife 2021;10:e68918 DO - 10.7554/eLife.68918 UR - https://doi.org/10.7554/eLife.68918 AB - 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. KW - chromosome compaction KW - mitosis KW - linker histone KW - nucleosome KW - Hi-C KW - chromatin JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -