Tyrosine phosphorylation of RNA Polymerase II CTD is associated with antisense promoter transcription and active enhancers in mammalian cells

  1. Nicolas Descostes
  2. Martin Heidemann
  3. Lionel Spinelli
  4. Roland Schüller
  5. Muhammad A Maqbool
  6. Romain Fenouil
  7. Frederic Koch
  8. Charlène Innocenti
  9. Marta Gut
  10. Ivo Gut
  11. Dirk Eick
  12. Jean-Christophe Andrau  Is a corresponding author
  1. Centre d'Immunologie de Marseille Luminy, Université Aix-Marseille, France
  2. Helmholtz Center Munich, Center of Integrated Protein Science Munich (CIPSM), Germany
  3. Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, France
  4. Institut de Génétique Moléculaire de Montpellier (IGMM), CNRS-UMR, France
  5. Max Planck Institute for Molecular Genetics, Germany
  6. Institut de Génomique Fonctionnelle, France
  7. Centre Nacional D'Anàlisi Genòmica, Spain
  8. Insitut de Génétique Moléculaire de Montpellier (IGMM), CNRS-UMR, France

Abstract

In mammals, the carboxy-terminal domain (CTD) of RNA polymerase (Pol) II consists of 52 conserved heptapeptide repeats containing the consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. Post-translational modifications of the CTD coordinate the transcription cycle and various steps of mRNA maturation. Here we describe Tyr1 phosphorylation (Tyr1P) as a hallmark of promoter (5' associated) Pol II in mammalian cells, in contrast to what was described in yeast. Tyr1P is predominantly found in antisense orientation at promoters but is also specifically enriched at active enhancers. Mutation of Tyr1 to phenylalanine (Y1F) prevents the formation of the hyper-phosphorylated Pol IIO form, induces degradation of Pol II to the truncated Pol IIB form and results in a lethal phenotype. Our results suggest that Tyr1P has evolved specialized and essential functions in higher eukaryotes associated with antisense promoter and enhancer transcription, and Pol II stability.

Article and author information

Author details

  1. Nicolas Descostes

    Centre d'Immunologie de Marseille Luminy, Université Aix-Marseille, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Martin Heidemann

    Helmholtz Center Munich, Center of Integrated Protein Science Munich (CIPSM), Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Lionel Spinelli

    Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, Marseilles, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Roland Schüller

    Helmholtz Center Munich, Center of Integrated Protein Science Munich (CIPSM), Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Muhammad A Maqbool

    Institut de Génétique Moléculaire de Montpellier (IGMM), CNRS-UMR, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Romain Fenouil

    Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, Marseilles, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Frederic Koch

    Max Planck Institute for Molecular Genetics, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Charlène Innocenti

    Institut de Génomique Fonctionnelle, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Marta Gut

    Centre Nacional D'Anàlisi Genòmica, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  10. Ivo Gut

    Centre Nacional D'Anàlisi Genòmica, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  11. Dirk Eick

    Helmholtz Center Munich, Center of Integrated Protein Science Munich (CIPSM), Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  12. Jean-Christophe Andrau

    Insitut de Génétique Moléculaire de Montpellier (IGMM), CNRS-UMR, Montpellier, France
    For correspondence
    jean-christophe.andrau@igmm.cnrs.fr
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2014, Descostes 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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  1. Nicolas Descostes
  2. Martin Heidemann
  3. Lionel Spinelli
  4. Roland Schüller
  5. Muhammad A Maqbool
  6. Romain Fenouil
  7. Frederic Koch
  8. Charlène Innocenti
  9. Marta Gut
  10. Ivo Gut
  11. Dirk Eick
  12. Jean-Christophe Andrau
(2014)
Tyrosine phosphorylation of RNA Polymerase II CTD is associated with antisense promoter transcription and active enhancers in mammalian cells
eLife 3:e02105.
https://doi.org/10.7554/eLife.02105

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https://doi.org/10.7554/eLife.02105

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