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Control of DNA methylation and heterochromatic silencing by histone H2B deubiquitination

Nature volume 447, pages 735738 (07 June 2007) | Download Citation

Abstract

Epigenetic regulation involves reversible changes in DNA methylation and/or histone modification patterns1,2,3,4,5,6,7. Short interfering RNAs (siRNAs) can direct DNA methylation and heterochromatic histone modifications, causing sequence-specific transcriptional gene silencing1,4,8,9. In animals and yeast, histone H2B is known to be monoubiquitinated, and this regulates the methylation of histone H3 (refs 10, 11). However, the relationship between histone ubiquitination and DNA methylation has not been investigated. Here we show that mutations in an Arabidopsis deubiquitination enzyme, SUP32/UBP26, decrease the dimethylation on lysine 9 of H3, suppress siRNA-directed methylation of DNA and release heterochromatic silencing of transgenes as well as transposons. We found that Arabidopsis histone H2B is monoubiquitinated at lysine 143 and that the levels of ubiquitinated H2B and trimethyl H3 at lysine 4 increase in sup32 mutant plants. SUP32/UBP26 can deubiquitinate H2B, and chromatin immunoprecipitation assays suggest an association between H2B ubiquitination and release of silencing. These data suggest that H2B deubiquitination by SUP32/UBP26 is required for heterochromatic histone H3 methylation and DNA methylation.

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Acknowledgements

We thank R. Martienssen and Z. Lippman for providing primer information for transposon analysis; Y. Zhang for advice on ChDIP and deubiquitination assays and critical reading of the manuscript; M. Osley and D. Gottschling for providing yeast strains; and T. Jenuwin for the gift of antibody against dimethyl H3K9. This work was supported by a US National Institutes of Health grant to J.-K.Z.

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Author notes

    • Vaniyambadi V. Sridhar
    •  & Avnish Kapoor

    These authors contributed equally to this work.

Affiliations

  1. Center for Plant Cell Biology and Department of Botany and Plant Sciences,

    • Vaniyambadi V. Sridhar
    • , Avnish Kapoor
    •  & Jian-Kang Zhu
  2. Mass Spectrometry Facility, Department of Chemistry, University of California, Riverside, California 92521, USA

    • Kangling Zhang
  3. Department of Horticulture and Landscape Architecture, Purdue University, West Lafayette, Indiana 47907, USA

    • Jianjun Zhu
    • , Tao Zhou
    • , Paul M. Hasegawa
    •  & Ray A. Bressan

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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 Jian-Kang Zhu.

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https://doi.org/10.1038/nature05864

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