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The enhancement of histone H4 and H2A serine 1 phosphorylation during mitosis and S-phase is evolutionarily conserved

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Abstract

Histone phosphorylation has long been associated with condensed mitotic chromatin; however, the functional roles of these modifications are not yet understood. Histones H1 and H3 are highly phosphorylated from late G2 through telophase in many organisms, and have been implicated in chromatin condensation and sister chromatid segregation. However, mutational analyses in yeast and biochemical experiments with Xenopus extracts have demonstrated that phosphorylation of H1 and H3 is not essential for such processes. In this study, we investigated additional histone phosphorylation events that may have redundant functions to H1 and H3 phosphorylation during mitosis. We developed an antibody to H4 and H2A that are phosphorylated at their respective serine 1 (S1) residues and found that H4S1/H2AS1 are highly phosphorylated in the mitotic chromatin of worm, fly, and mammals. Mitotic H4/H2A phosphorylation has similar timing and localization as H3 phosphorylation, and closely correlates with the chromatin condensation events during mitosis. We also detected a lower level of H4/H2A phosphorylation in 5-bromo-2-deoxyuridine-positive S-phase cells, which corroborates earlier studies that identified H4S1 phosphorylation on newly synthesized histones during S-phase. The evolutionarily conserved phosphorylation of H4/H2A during the cell cycle suggests that they may have a dual purpose in chromatin condensation during mitosis and histone deposition during S-phase.

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Acknowledgements

We graciously thank Jeffrey Hayes and Christophe Thiret of the University of Rochester, and Wang L. Cheung of the University of Virginia for sharing the results of their unpublished data. This work was supported by grants from the National Institutes of Health to C.D.A. (GM40922) and D.F.H. (GM37537).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, VA 22908, USA

    Cynthia M. Barber, Fiona B. Turner & Sean D. Taverna

  2. Laboratory of Chromatin Biology, The Rockefeller University, New York, NY 10021, USA

    Yanming Wang, Sean D. Taverna & C. David Allis

  3. Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA

    Kirsten Hagstrom & Barbara J. Meyer

  4. Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, M5G 2M9, Canada

    Peter Cheung

  5. Department of Chemistry, University of Virginia, Charlottesville, VA 22908, USA

    Sahana Mollah, Beatrix Ueberheide & Donald F. Hunt

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  1. Cynthia M. Barber
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  2. Fiona B. Turner
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  3. Yanming Wang
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  11. C. David Allis
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Correspondence to C. David Allis.

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Communicated by G. Almouzni

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Barber, C.M., Turner, F.B., Wang, Y. et al. The enhancement of histone H4 and H2A serine 1 phosphorylation during mitosis and S-phase is evolutionarily conserved. Chromosoma 112, 360–371 (2004). https://doi.org/10.1007/s00412-004-0281-9

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  • DOI: https://doi.org/10.1007/s00412-004-0281-9

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