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

Walther, Nike, Hossain, M. Julius, Politi, Antonio Z., Koch, Birgit, Kueblbeck, Moritz, Ødegård-Fougner, Øyvind, Lampe, Marko and Ellenberg, Jan (2018) A quantitative map of human Condensins provides new insights into mitotic chromosome architecture. Journal of Cell Biology, 217 (7), 2309-2328. (doi:10.1083/jcb.201801048).

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.

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Contributors

Author: M. Julius Hossain

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