Abstract
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.
Highlights
Genomic DNA in eukaryotes is compacted by orders of magnitude over its linear length
Depletion of linker histone H1.8 in Xenopus egg extracts makes chromosomes thinner and elongated. We asked if this phenotype may reflect the potential role of H1.8 in regulating condensins and TOP2A, which are essential for mitotic chromosome compaction in Xenopus egg extracts (Hirano and Mitchison, 1994; Adachi et al, 1991; Cuvier and Hirano, 2003)
It has been reported that H1.8 depletion does not affect chromosomal enrichment of major chromatin proteins (Maresca et al, 2005), we attempted to quantify chromatin-bound levels of condensins and TOP2A
Summary
Genomic DNA in eukaryotes is compacted by orders of magnitude over its linear length. The extent and mode of the packaging change between interphase and mitosis to support the cell cycle- dependent functions of the DNA. While loosely packed DNA allows efficient decoding of genetic information in interphase, mitotic compaction of DNA enables efficient distribution of genetic information to daughter cells. Chromosome individualization during mitosis ensures that all duplicated chromosomes are independently moved by microtubules and are distributed to daughter cells. Despite these common functional requirements of mitotic chromosomes and evolutionary conservation of major known regulators of mitotic chromosome structures, the size and shape of chromosomes vary among species and developmental stages. During early embryogenesis in Xenopus and Caenorhabditis elegans, mitotic chromosome lengths become shorter
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