Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks

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Abstract
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. 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.