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Cellular and Molecular Life Sciences

, Volume 74, Issue 18, pp 3305–3315 | Cite as

Protein arginine methylation: a prominent modification and its demethylation

  • Juste Wesche
  • Sarah Kühn
  • Benedikt M. Kessler
  • Maayan Salton
  • Alexander Wolf
Review

Abstract

Arginine methylation of histones is one mechanism of epigenetic regulation in eukaryotic cells. Methylarginines can also be found in non-histone proteins involved in various different processes in a cell. An enzyme family of nine protein arginine methyltransferases catalyses the addition of methyl groups on arginines of histone and non-histone proteins, resulting in either mono- or dimethylated-arginine residues. The reversibility of histone modifications is an essential feature of epigenetic regulation to respond to changes in environmental factors, signalling events, or metabolic alterations. Prominent histone modifications like lysine acetylation and lysine methylation are reversible. Enzyme family pairs have been identified, with each pair of lysine acetyltransferases/deacetylases and lysine methyltransferases/demethylases operating complementarily to generate or erase lysine modifications. Several analyses also indicate a reversible nature of arginine methylation, but the enzymes facilitating direct removal of methyl moieties from arginine residues in proteins have been discussed controversially. Differing reports have been seen for initially characterized putative candidates, like peptidyl arginine deiminase 4 or Jumonji-domain containing protein 6. Here, we review the most recent cellular, biochemical, and mass spectrometry work on arginine methylation and its reversible nature with a special focus on putative arginine demethylases, including the enzyme superfamily of Fe(II) and 2-oxoglutarate-dependent oxygenases.

Keywords

Histone modifications Post-translational modifications KDM KMT KDM2A KDM3A KDM4E KDM5C KDM6B PHF8 KDM7B Liquid chromatography–tandem mass spectrometry 

Notes

Acknowledgements

We are grateful to Angelika Böttger and Joel Schick for useful comments on the manuscript.

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© Springer International Publishing 2017

Authors and Affiliations

  1. 1.Institute of Molecular Toxicology and PharmacologyHelmholtz Zentrum München-German Research Center for Environmental HealthNeuherbergGermany
  2. 2.Nuffield Department of Medicine, Target Discovery InstituteUniversity of OxfordOxfordUK
  3. 3.Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel-CanadaHebrew University-Hadassah Medical SchoolJerusalemIsrael

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