Medical Institute of Bioregulation, Kyushu University

Title

Approaching Mitotic Chromosome Formation from All Directions

Speaker

William C. Earnshaw, PhD, FRS, NAS
Professor Emeritus
University of Edinburgh

Date

Nov. 6 (Fri), 2026
15:00–16:00

Venue

Seminar Room 104, 1F, Biomedical Research Station, Hospital Campus
(Building No. 35 on the [Campus Map])

Abstract

Attempts to understand how the DNA is packaged in mitotic chromosomes are confounded by the huge size of the DNA, the incredible chromatin density in mitotic chromosomes and the complexity of the machinery that does the DNA packaging. We study this problem by combining chemical genetics, Hi-C genomic analysis, polymer modelling, light and electron microscopy and proteomics. In our system, an entire cell population of chicken DT40 lymphocytes enters mitosis with near perfect synchrony within 2 to 3 minutes of release of a G2 phase arrest. This allows us to “kinetically section” the process and perform biochemical and structural analyses with minute-by-minute resolution. The cells can be engineered so that chromosome formation is directed by single SMC complexes: cohesin, condensin I or condensin II. Our latest models suggest that chromosomes are a disorderly helix of loops created by the SMC complexes. Condensin II drives the formation of cylindrical chromosomes but is restrained from achieving its ideal state by residual cohesive cohesin. Our electron microscopy analysis in human cells reveals that nucleosomes achieve a near millimolar concentration in mitotic chromosomes. The data from our electron microscopy and modelling are most consistent with chromosome formation involving a combination of looping by SMC complexes and chromatin phase separation. However, the chromatin concentration in chromosomes is higher than the concentration of nucleosomes in phase-separated droplets in vitro. The mechanism responsible for this compaction of the chromatin is unknown and we have recently obtained evidence inconsistent with all previous models for how the compaction is achieved. Preliminary evidence suggests that a preference of condensin I for G:C_rich DNA may drive a radial organisation where A:T-rich DNA is preferentially located towards the chromosome periphery. Despite over 140 years of study, the essential mysteries of mitotic chromosome formation remain elusive.

References

• J.H. Gibcus^*, K. Samejima^*, A. Goloborodko^*, I. Samejima, N. Naumova, J. Nuebler, M. Kanemaki, L. Xie, J.R. Paulson, W.C. Earnshaw^†, L.A. Mirny^† & J. Dekker^†. A pathway for mitotic chromosome formation. Science. 2018 Feb 9;359(6376):eaao6135. doi: 10.1126/science.aao6135.
• F. Cisneros-Soberanis^†, E. Simpson^†, A.J. Beckett, N. Pucekova, S. Corless, N.Y. Kochanova, I.A. Prior, D.G. Booth^* & W.C. Earnshaw^*. J Cell Biol. 2024 Nov 4;223(11):e202403165. doi: 10.1083/jcb.202403165.
• K. Samejima^†, J.H. Gibcus^†, S. Abraham^‡, F. Cisneros-Soberanis^‡, I. Samejima^‡, A.J. Beckett, N. Pučeková, M. Alba Abad, C. Spanos, B. Medina-Pritchard, J.R. Paulson, L. Xie, A.A. Jeyaprakash, I.A. Prior, L.A. Mirny^*, J. Dekker^*, A. Goloborodko^* & W.C. Earnshaw^*. Rules of engagement for condensins and cohesins guide mitotic chromosome formation. Science. 2025 Apr 11;388(6743):eadq1709. doi: 10.1126/science.adq1709.
• N.Y. Kochanova^†, M. Deb^†, M. Borsò^†, S. Webb, I. Ustun, K. Samejima, I. Forne, I. Samejima, C. Reid, L. Xie, J.R. Paulson, A. Imhof^* & W.C. Earnshaw^*. A time-resolved atlas of histone modifications during mitotic entry. Mol Cell. 2026 May 7;86(9):1653-1672.e9. doi: 10.1016/j.molcel.2026.03.038.

Contact

Noriko Saitoh
Division of Cancer Genome Biology, Medical Institute of Bioregulation
E-mail: saitoh.noriko.885[＠]m.kyushu-u.ac.jp
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