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.

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.

Keywords: Hi-C; chromatin; chromosome compaction; chromosomes; gene expression; linker histone; mitosis; nucleosome; xenopus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Animals
  • Cell Extracts / chemistry
  • Chromatin / metabolism*
  • Chromosomes / genetics*
  • Chromosomes / ultrastructure
  • DNA Topoisomerases, Type II / genetics*
  • DNA-Binding Proteins / metabolism
  • Female
  • Histones / genetics*
  • Models, Biological
  • Multiprotein Complexes / metabolism
  • Oocytes / chemistry
  • Oocytes / metabolism
  • Spindle Apparatus / genetics
  • Spindle Apparatus / pathology
  • Spindle Apparatus / ultrastructure
  • Xenopus laevis

Substances

  • Cell Extracts
  • Chromatin
  • DNA-Binding Proteins
  • Histones
  • Multiprotein Complexes
  • condensin complexes
  • Adenosine Triphosphatases
  • DNA Topoisomerases, Type II

Associated data

  • GEO/GSE164434