Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks (original) (raw)

Nature volume 456, pages 125–129 (2008)Cite this article

Abstract

Eukaryotic chromatin is separated into functional domains differentiated by post-translational histone modifications, histone variants and DNA methylation1,2,3,4,5,6. Methylation is associated with repression of transcriptional initiation in plants and animals, and is frequently found in transposable elements. Proper methylation patterns are crucial for eukaryotic development4,5, and aberrant methylation-induced silencing of tumour suppressor genes is a common feature of human cancer7. In contrast to methylation, the histone variant H2A.Z is preferentially deposited by the Swr1 ATPase complex near 5′ ends of genes where it promotes transcriptional competence8,9,10,11,12,13,14,15,16,17,18,19,20. How DNA methylation and H2A.Z influence transcription remains largely unknown. Here we show that in the plant Arabidopsis thaliana regions of DNA methylation are quantitatively deficient in H2A.Z. Exclusion of H2A.Z is seen at sites of DNA methylation in the bodies of actively transcribed genes and in methylated transposons. Mutation of the MET1 DNA methyltransferase, which causes both losses and gains of DNA methylation4,5, engenders opposite changes (gains and losses) in H2A.Z deposition, whereas mutation of the PIE1 subunit of the Swr1 complex that deposits H2A.Z17 leads to genome-wide hypermethylation. Our findings indicate that DNA methylation can influence chromatin structure and effect gene silencing by excluding H2A.Z, and that H2A.Z protects genes from DNA methylation.

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Gene Expression Omnibus

Data deposits

Microarray data are deposited in the GEO database under accession number GSE12212.

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Acknowledgements

We thank J. Henikoff and B. Nguyen for help with computational analyses, P. Talbert for assistance with cytology, T. Bryson and A. Morgan for technical support, M. Gehring and B. Staskawicz for the root culture protocol, R. Deal and R. Meagher for H2A.Z antibodies, the FHCRC DNA array facility for carrying out microarray hybridizations, and M. Orozco for transgenic lines. D.C.-D. is supported by an NSF predoctoral fellowship. D.Z. is a Leukemia and Lymphoma Society fellow.

Author Contributions D.Z. and S.H. conceived the study; D.Z. and D.C.-D. performed the experiments; D.Z., T.B., D.C.-D. and S.H. analysed the data; and D.Z. and S.H. wrote the paper.

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Authors and Affiliations

  1. University of California, 211 Koshland Hall, Berkeley, California 94720, USA ,
    Daniel Zilberman & Devin Coleman-Derr
  2. Fred Hutchinson Cancer Research Center, and,,
    Tracy Ballinger & Steven Henikoff
  3. Howard Hughes Medical Institute, 1100 Fairview Avenue North, Seattle, Washington 98109, USA ,
    Tracy Ballinger & Steven Henikoff

Authors

  1. Daniel Zilberman
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  2. Devin Coleman-Derr
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  3. Tracy Ballinger
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  4. Steven Henikoff
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Corresponding authors

Correspondence toDaniel Zilberman or Steven Henikoff.

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Zilberman, D., Coleman-Derr, D., Ballinger, T. et al. Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks.Nature 456, 125–129 (2008). https://doi.org/10.1038/nature07324

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Editorial Summary

Plant chromatin: DNA methylation versus histone H2A.Z

Although DNA methylation has been actively studied for several decades, the mechanism by which it causes gene silencing remains largely unknown. In contrast to DNA methylation, the histone variant H2A.Z promotes transcriptional competence in plants, animals and fungi. This paper reports the finding that regions of DNA methylation in the Arabidopsis thaliana genome are deficient in H2A.Z. DNA methylation appears to repress transcription by exclusion of H2A.Z. This suggets a novel relationship between a covalent modification of DNA and a core nucleosome component with an important role in organizing eukaryotic chromatin.