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Histone H3 tail clipping regulates gene expression

Nature Structural & Molecular Biology volume 16, pages 1722 (2009) | Download Citation

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Abstract

Induction of gene expression in yeast and human cells involves changes in the histone modifications associated with promoters. Here we identify a histone H3 endopeptidase activity in Saccharomyces cerevisiae that may regulate these events. The endopeptidase cleaves H3 after Ala21, generating a histone that lacks the first 21 residues and shows a preference for H3 tails carrying repressive modifications. In vivo, the H3 N terminus is clipped, specifically within the promoters of genes following the induction of transcription. H3 clipping precedes the process of histone eviction seen when genes become fully active. A truncated H3 product is not generated in yeast carrying a mutation of the endopeptidase recognition site (H3 Q19A L20A) and gene induction is defective in these cells. These findings identify clipping of H3 tails as a previously uncharacterized modification of promoter-bound nucleosomes, which may result in the localized clearing of repressive signals during the induction of gene expression.

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Acknowledgements

We thank B. Xhemalce for constructive discussions, L. Packman for excellent assistance with peptide and calf H3 sequencing and A. Verreault (Institute for Research in Immunology and Cancer, Université de Montréal) for the gift of H3 and H4 antibodies. We are most grateful to M. Dickman, M. Vermeulen and M. Mann, H. Erdjument-Bromage, P. Tempst, S. Tully, B.F. Cravatt and S.Y. Peak-Chew for their attempts to identify the H3 endopeptidase by MS.

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Affiliations

  1. Gurdon Institute and Department of Pathology, Tennis Court Road, Cambridge CB2 1QN, UK.

    • Helena Santos-Rosa
    • , Antonis Kirmizis
    • , Christopher Nelson
    • , Till Bartke
    •  & Tony Kouzarides
  2. Laval University Cancer Research Center, Hôtel-Dieu de Québec (CHUQ), 9 McMahon Street, Quebec City, Quebec G1R-2J6, Canada.

    • Nehme Saksouk
    •  & Jacques Cote

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Competing interests

T.K. is a director of Abcam Plc.

Corresponding author

Correspondence to Tony Kouzarides.

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DOI

https://doi.org/10.1038/nsmb.1534

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