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Loss of Drosophila Myb interrupts the progression of chromosome condensation

Nature Cell Biology volume 9, pages 581–587 (2007)Cite this article

Abstract

Completion of chromosome condensation is required before segregation during the mitotic cell cycle to ensure the transmission of genetic material with high fidelity in a timely fashion. In many eukaryotes this condensation is regulated by phosphorylation of histone H3 on Ser 10 (H3S10). This phosphorylation normally begins in the late-replicating pericentric heterochromatin and then spreads to the earlier replicating euchromatin. Here, we show that these phases of condensation are genetically separable in that the absence of Drosophila Myb causes cells to arrest with H3S10 phosphorylation of heterochromatin but not euchromatin. In addition, we used mosaic analysis to demonstrate that although the Myb protein can be removed in a single cell cycle, the failure of chromosome condensation occurs only after many cell divisions in the absence of Myb protein. The Myb protein is normally located in euchromatic but not heterochromatic regions of the nucleus, suggesting that Myb may be essential for a modification of euchromatin that is required for the efficient spread of chromosome condensation.

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Figure 1: Chromosome condensation abnormalities in Drosophila Myb-null eye imaginal discs.
Figure 2: Compartment-specific rescue reveals an increased frequency of cells with PH3-positive heterochromatin in the absence of Myb.
Figure 3: Compartment-specific rescue reveals a defect in the progression of chromosome condensation in the absence of Myb.
Figure 4: A functional GFP–Myb fusion protein localizes to euchromatin, not heterochromatin.
Figure 5: Myb is required for a chromatin mark essential for progression of chromosome condensation.

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Acknowledgements

This work was supported by the United States Public Health Service (USPHS) grant R01 CA90307 (J.S.L.). We thank S. Heidmann, members of the Botchan laboratory, and the other members of the Lipsick laboratory for helpful discussions and for sharing reagents.

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Authors and Affiliations

  1. Departments of Pathology and of Genetics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, 94305–5342, CA, USA

    J. Robert Manak, Hong Wen, Tran Van, Laura Andrejka & Joseph S. Lipsick

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Contributions

All authors contributed to the experimental work. The experiments were planned by J.R.M., H.W. and J.S.L. The manuscript was written by J.R.M. and J.S.L.

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Correspondence to Joseph S. Lipsick.

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The authors declare no competing financial interests.

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Manak, J., Wen, H., Van, T. et al. Loss of Drosophila Myb interrupts the progression of chromosome condensation. Nat Cell Biol 9, 581–587 (2007). https://doi.org/10.1038/ncb1580

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