A quantitative map of human Condensins provides new insights into mitotic chromosome architecture

J Cell Biol. 2018 Jul 2;217(7):2309-2328. doi: 10.1083/jcb.201801048. Epub 2018 Apr 9.

Abstract

The two Condensin complexes in human cells are essential for mitotic chromosome structure. We used homozygous genome editing to fluorescently tag Condensin I and II subunits and mapped their absolute abundance, spacing, and dynamic localization during mitosis by fluorescence correlation spectroscopy (FSC)-calibrated live-cell imaging and superresolution microscopy. Although ∼35,000 Condensin II complexes are stably bound to chromosomes throughout mitosis, ∼195,000 Condensin I complexes dynamically bind in two steps: prometaphase and early anaphase. The two Condensins rarely colocalize at the chromatid axis, where Condensin II is centrally confined, but Condensin I reaches ∼50% of the chromatid diameter from its center. Based on our comprehensive quantitative data, we propose a three-step hierarchical loop model of mitotic chromosome compaction: Condensin II initially fixes loops of a maximum size of ∼450 kb at the chromatid axis, whose size is then reduced by Condensin I binding to ∼90 kb in prometaphase and ∼70 kb in anaphase, achieving maximum chromosome compaction upon sister chromatid segregation.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Anaphase / genetics
  • Chromatids / genetics
  • Chromosome Segregation / genetics*
  • Chromosomes / genetics*
  • DNA-Binding Proteins / genetics*
  • Gene Editing
  • Humans
  • Mitosis / genetics*
  • Multiprotein Complexes / genetics*

Substances

  • DNA-Binding Proteins
  • Multiprotein Complexes
  • condensin complexes
  • Adenosine Triphosphatases