Genomic location of PRMT6-dependent H3R2 methylation is linked to the transcriptional outcome of associated genes

Caroline Bouchard, Peeyush Sahu, Marion Meixner, René Reiner Nötzold, Marco B. Rust, Elisabeth Kremmer, Regina Feederle, Gene Hart-Smith, Florian Finkernagel, Marek Bartkuhn, Soni Savai Pullamsetti, Andrea Nist, Thorsten Stiewe, Sjaak Philipsen, Uta Maria Bauer*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Citations (Scopus)
4 Downloads (Pure)

Abstract

Protein arginine methyltransferase 6 (PRMT6) catalyzes asymmetric dimethylation of histone H3 at arginine 2 (H3R2me2a). This mark has been reported to associate with silent genes. Here, we use a cell model of neural differentiation, which upon PRMT6 knockout exhibits proliferation and differentiation defects. Strikingly, we detect PRMT6-dependent H3R2me2a at active genes, both at promoter and enhancer sites. Loss of H3R2me2a from promoter sites leads to enhanced KMT2A binding and H3K4me3 deposition together with increased target gene transcription, supporting a repressive nature of H3R2me2a. At enhancers, H3R2me2a peaks co-localize with the active enhancer marks H3K4me1 and H3K27ac. Here, loss of H3R2me2a results in reduced KMT2D binding and H3K4me1/H3K27ac deposition together with decreased transcription of associated genes, indicating that H3R2me2a also exerts activation functions. Our work suggests that PRMT6 via H3R2me2a interferes with the deposition of adjacent histone marks and modulates the activity of important differentiation-associated genes by opposing transcriptional effects.

Original languageEnglish
Pages (from-to)3339-3352
Number of pages14
JournalCell Reports
Volume24
Issue number12
DOIs
Publication statusPublished - 18 Sep 2018
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • protein arginine methyltransferases
  • histone modifications
  • posttranslational modifications
  • histone code
  • histone arginine methylation
  • chromatin
  • transcriptional regulation
  • gene expression
  • pluripotency
  • neural differentiation

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  • Cite this

    Bouchard, C., Sahu, P., Meixner, M., Nötzold, R. R., Rust, M. B., Kremmer, E., ... Bauer, U. M. (2018). Genomic location of PRMT6-dependent H3R2 methylation is linked to the transcriptional outcome of associated genes. Cell Reports, 24(12), 3339-3352. https://doi.org/10.1016/j.celrep.2018.08.052