Open Access Research

Methylation of H2AR29 is a novel repressive PRMT6 target

Tanja Waldmann14, Annalisa Izzo1, Kinga Kamieniarz1, Florian Richter1, Christine Vogler1, Bettina Sarg2, Herbert Lindner2, Nicolas L Young3, Gerhard Mittler1, Benjamin A Garcia3 and Robert Schneider1*

Author Affiliations

1 MPI for Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany

2 Innsbruck Medical University, Division of Clinical Biochemistry, Biocenter, Fritz-Pregl-Str. 3, 6020 Innsbruck, Austria

3 Princeton University, Department of Molecular Biology, 415 Shultz Laboratory, Princeton, NJ 08540, USA

4 University of Konstanz, Doerenkamp-Zbinden chair, Universitätsstr. 10, 78457 Konstanz, Germany

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Epigenetics & Chromatin 2011, 4:11  doi:10.1186/1756-8935-4-11

Published: 20 July 2011

Abstract

Background

Covalent histone modifications are central to all DNA-dependent processes. Modifications of histones H3 and H4 are becoming well characterised, but knowledge of how H2A modifications regulate chromatin dynamics and gene expression is still very limited.

Results

To understand the function of H2A modifications, we performed a systematic analysis of the histone H2A methylation status. We identified and functionally characterised two new methylation sites in H2A: R11 (H2AR11) and R29 (H2AR29). Using an unbiased biochemical approach in combination with candidate assays we showed that protein arginine methyltransferase (PRMT) 1 and PRMT6 are unique in their ability to catalyse these modifications. Importantly we found that H2AR29me2 is specifically enriched at genes repressed by PRMT6, implicating H2AR29me2 in transcriptional repression.

Conclusions

Our data establishes R11 and R29 as new arginine methylation sites in H2A. We identified the specific modifying enzymes involved, and uncovered a novel functional role of H2AR29me2 in gene silencing in vivo. Thus this work reveals novel insights into the function of H2A methylation and in the mechanisms of PRMT6-mediated transcriptional repression.