1. Computational and Systems Biology
  2. Chromosomes and Gene Expression
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Methylation of RNA polymerase II non-consensus Lysine residues marks early transcription in mammalian cells

  1. João D Dias
  2. Tiago Rito
  3. Elena Torlai Triglia
  4. Alexander Kukalev
  5. Carmelo Ferrai
  6. Mita Chotalia
  7. Emily Brookes
  8. Hiroshi Kimura
  9. Ana Pombo  Is a corresponding author
  1. Max-Delbrück Centre for Molecular Medicine, Germany
  2. Imperial College London, United Kingdom
  3. University College London, United Kingdom
  4. Tokyo Institute of Technology, Japan
Research Article
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Cite this article as: eLife 2015;4:e11215 doi: 10.7554/eLife.11215

Abstract

Dynamic post-translational modification of RNA polymerase II (RNAPII) coordinates the co-transcriptional recruitment of enzymatic complexes that regulate chromatin states and processing of nascent RNA. Extensive phosphorylation of serine residues at the largest RNAPII subunit occurs at its structurally-disordered C-terminal domain (CTD), which is composed of multiple heptapeptide repeats with consensus sequence Y1-S2-P3-T4-S5-P6-S7. Serine-5 and Serine-7 phosphorylation mark transcription initiation, whereas Serine-2 phosphorylation coincides with productive elongation. In vertebrates, the CTD has eight non-canonical substitutions of Serine-7 into Lysine-7, which can be acetylated (K7ac). Here, we describe mono- and di-methylation of CTD Lysine-7 residues (K7me1 and K7me2). K7me1 and K7me2 are observed during the earliest transcription stages and precede or accompany Serine-5 and Serine-7 phosphorylation. In contrast, K7ac is associated with RNAPII elongation, Serine-2 phosphorylation and mRNA expression. We identify an unexpected balance between RNAPII K7 methylation and acetylation at gene promoters, which fine-tunes gene expression levels.

Article and author information

Author details

  1. João D Dias

    Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Tiago Rito

    Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Elena Torlai Triglia

    Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Alexander Kukalev

    Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Carmelo Ferrai

    Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Mita Chotalia

    Genome Function Group, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Emily Brookes

    MRC Laboratory for Molecular and Cell Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Hiroshi Kimura

    Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan
    Competing interests
    The authors declare that no competing interests exist.
  9. Ana Pombo

    Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin, Germany
    For correspondence
    ana.pombo@mdc-berlin.de
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All handling of mice was approved by the Hokkaido University Animal Experiment Committee (approval number: 11-0109) and carried out according to guidelines for animal experimentation at Hokkaido University, where MAB Institute Inc. is located. Animals were housed in a designated pathogen-free facility at Hokkaido University. Mice were humanely euthanized via cervical dislocation by technically proficient individuals.

Reviewing Editor

  1. Nick J Proudfoot, University of Oxford, United Kingdom

Publication history

  1. Received: August 30, 2015
  2. Accepted: December 18, 2015
  3. Accepted Manuscript published: December 19, 2015 (version 1)
  4. Version of Record published: February 8, 2016 (version 2)

Copyright

© 2015, Dias et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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