Article | Published:

Histone H2A.Z inheritance during the cell cycle and its impact on promoter organization and dynamics

Nature Structural & Molecular Biology volume 19, pages 10761083 (2012) | Download Citation

Abstract

Although it has been clearly established that well-positioned histone H2A.Z–containing nucleosomes flank the nucleosome-depleted region (NDR) at the transcriptional start site (TSS) of active mammalian genes, how this chromatin-based information is transmitted through the cell cycle is unknown. We show here that in mouse trophoblast stem cells, the amount of histone H2A.Z at promoters decreased during S phase, coinciding with homotypic (H2A.Z–H2A.Z) nucleosomes flanking the TSS becoming heterotypic (H2A.Z–H2A). To our surprise these nucleosomes remained heterotypic at M phase. At the TSS, we identified an unstable heterotypic histone H2A.Z–containing nucleosome in G1 phase that was lost after DNA replication. These dynamic changes at the TSS mirror a global expansion of the NDR at S and M phases, which, unexpectedly, is unrelated to transcriptional activity. Coincident with the loss of histone H2A.Z at promoters, histone H2A.Z is targeted to the centromere when mitosis begins.

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Acknowledgements

We thank M. Day (University of Sydney) for providing us with trophoblast stem cells and advice on their maintenance. We acknowledge the excellent high-throughput DNA sequencing service provided by our in house Biomolecular Research Service headed by S. Palmer. We thank D. Ryan for his help with the quantification of histone H2A.Z at the different stages of the cell cycle and H. French for early help in analyzing the microarray data. This work was supported by Australian National Health and Medical Research Council project grants to T.A.S. and D.J.T. (1009851), and M.N. and D.J.T. (1009850).

Author information

Author notes

    • Rohan Williams

    Present address: Singapore Centre on Environmental Life Sciences Engineering, National University of Singapore, Singapore.

    • Jana Amrichova
    •  & Brian J Parker

    These authors contributed equally to this work.

Affiliations

  1. The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.

    • Maxim Nekrasov
    • , Jana Amrichova
    • , Brian J Parker
    • , Tatiana A Soboleva
    • , Cameron Jack
    • , Rohan Williams
    • , Gavin A Huttley
    •  & David J Tremethick

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Contributions

M.N. performed and helped design the experiments. J.A. carried out the cell-synchronization experiments. T.A.S. established the trophoblast stem cell system and performed the human U20S cell synchronization experiments. R.W. developed and performed data analysis of global mouse gene expression data. G.A.H. designed and contributed to interpretation of the analysis of the Illumina short read data. C.J. assisted with the design and executed the analyses of Illumina short read data. B.J.P. designed and contributed to the interpretation of the computational analysis of CTCF binding sites. D.J.T. conceived the project, helped design the experiments and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to David J Tremethick.

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DOI

https://doi.org/10.1038/nsmb.2424

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