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Amplification of histone genes by circular chromosome formation in Saccharomyces cerevisiae

Nature volume 443, pages 10031007 (26 October 2006) | Download Citation

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Abstract

Proper histone levels are critical for transcription, chromosome segregation, and other chromatin-mediated processes1–7. In Saccharomyces cerevisiae, the histones H2A and H2B are encoded by two gene pairs, named HTA1-HTB1 and HTA2-HTB2 (ref. 8). Previous studies have demonstrated that when HTA2-HTB2 is deleted, HTA1-HTB1 dosage compensates at the transcriptional level4,9. Here we show that a different mechanism of dosage compensation, at the level of gene copy number, can occur when HTA1-HTB1 is deleted. In this case, HTA2-HTB2 amplifies via creation of a new, small, circular chromosome. This duplication, which contains 39 kb of chromosome II, includes HTA2-HTB2, the histone H3-H4 locus HHT1-HHF1, a centromere and origins of replication. Formation of the new chromosome occurs by recombination between two Ty1 retrotransposon elements that flank this region. Following meiosis, recombination between these two particular Ty1 elements occurs at a greatly elevated level in hta1-htb1Δ mutants, suggesting that a decreased level of histones H2A and H2B specifically stimulates this amplification of histone genes. Our results demonstrate another mechanism by which histone gene dosage is controlled to maintain genomic integrity.

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Acknowledgements

We thank A. Dudley and D. Helmlinger for helpful comments on the manuscript. We also thank J. Haber and J.-A. Kim for the suggestion of and advice on the HO experiment, and V. Dror for instruction about CHEF gels. We are grateful to A. Gabriel, P. Kaufman, M. A. Osley and T. Petes for sharing unpublished results and for discussions. We thank J. Hirschhorn, whose observations led to this project. This work was supported by a grant from the National Institutes of Health to F.W. and by a National Science Foundation Graduate Fellowship to D.E.L.

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  1. Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA

    • Diana E. Libuda
    •  & Fred Winston

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Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Corresponding author

Correspondence to Fred Winston.

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    This file contains Supplementary Discussion, Supplementary Methods, Supplementary Tables 1–6 and Supplementary Figures 1–7.

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https://doi.org/10.1038/nature05205

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