Article | Published:

SMC complexes differentially compact mitotic chromosomes according to genomic context

Nature Cell Biology volume 19, pages 10711080 (2017) | Download Citation

Abstract

Structural maintenance of chromosomes (SMC) protein complexes are key determinants of chromosome conformation. Using Hi-C and polymer modelling, we study how cohesin and condensin, two deeply conserved SMC complexes, organize chromosomes in the budding yeast Saccharomyces cerevisiae. The canonical role of cohesin is to co-align sister chromatids, while condensin generally compacts mitotic chromosomes. We find strikingly different roles for the two complexes in budding yeast mitosis. First, cohesin is responsible for compacting mitotic chromosome arms, independently of sister chromatid cohesion. Polymer simulations demonstrate that this role can be fully accounted for through cis-looping of chromatin. Second, condensin is generally dispensable for compaction along chromosome arms. Instead, it plays a targeted role compacting the rDNA proximal regions and promoting resolution of peri-centromeric regions. Our results argue that the conserved mechanism of SMC complexes is to form chromatin loops and that distinct SMC-dependent looping activities are selectively deployed to appropriately compact chromosomes.

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Acknowledgements

We thank B. Lajoie and J. Gibcus for aid in processing the Hi-C data sets. We thank L. Aragon, K. Nasmyth and J. Diffley for yeast strains. This work was funded by the Biotechnology and Biological Sciences Research Council United Kingdom (BBSRC UK) Grant ref. BB/J018554/1 (S.A.S., M.Y.), the Royal Society UK (J.B.), NIH U54 4D Nucleome grant (DK107980) and NIH R01 (HG003143) (A.G., G.F., J.M.B., L.M., and J.D.). J.D. in an investigator of the Howard Hughes Medical Institute.

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Author notes

    • Stephanie Andrea Schalbetter
    • , Anton Goloborodko
    •  & Geoffrey Fudenberg

    These authors contributed equally to this work.

Affiliations

  1. Genome Damage and Stability Centre, Science Park Road, University of Sussex, Falmer, Brighton BN1 9RQ, UK

    • Stephanie Andrea Schalbetter
    • , Catrina Miles
    • , Miao Yu
    •  & Jonathan Baxter
  2. Program in Systems Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA

    • Jon-Matthew Belton
    •  & Job Dekker
  3. Institute for Medical Engineering and Sciences, Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Anton Goloborodko
    • , Geoffrey Fudenberg
    •  & Leonid Mirny

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Contributions

S.A.S. performed all cell culture and generated Hi-C libraries. A.G. analysed sequenced libraries and Hi-C data sets. G.F. modelled chromosome conformation of the budding yeast nucleus with help from A.G. J.M.B. guided Hi-C library instruction and analysed sequenced libraries. M.Y. and C.M. constructed and characterized the inducible condensin alleles. J.D. advised on study construction and guided processing and analysis of Hi-C data sets. L M. guided the modelling of the Hi-C data. J.B. conceived and coordinated the study. J.B., G.F. and A.G. wrote the manuscript with input from S.A.S., L.M. and J.D.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Jonathan Baxter.

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https://doi.org/10.1038/ncb3594

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