FBXL19 recruits CDK-Mediator to CpG islands of developmental genes priming them for activation during lineage commitment

  1. Emilia A Dimitrova
  2. Takashi Kondo
  3. Angelika Feldmann
  4. Manabu Nakayama
  5. Yoko Koseki
  6. Rebecca Konietzny
  7. Benedikt M Kessler
  8. Haruhiko Koseki
  9. Robert J Klose  Is a corresponding author
  1. University of Oxford, United Kingdom
  2. RIKEN Center for Integrative Medical Sciences, Japan
  3. Kazusa DNA Research Institute, Japan

Abstract

CpG islands are gene regulatory elements associated with the majority of mammalian promoters, yet how they regulate gene expression remains poorly understood. Here, we identify FBXL19 as a CpG island-binding protein in mouse embryonic stem (ES) cells and show that it associates with the CDK-Mediator complex. We discover that FBXL19 recruits CDK-Mediator to CpG island-associated promoters of non-transcribed developmental genes to prime these genes for activation during cell lineage commitment. We further show that recognition of CpG islands by FBXL19 is essential for mouse development. Together this reveals a new CpG island-centric mechanism for CDK-Mediator recruitment to developmental gene promoters in ES cells and a requirement for CDK-Mediator in priming these developmental genes for activation during cell lineage commitment.

Data availability

Sequencing data generated in this study have been deposited in GEO under accession code GSE98756

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Emilia A Dimitrova

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Takashi Kondo

    Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
    Competing interests
    The authors declare that no competing interests exist.
  3. Angelika Feldmann

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Manabu Nakayama

    Department of Technology Development, Kazusa DNA Research Institute, Kisarazu, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Yoko Koseki

    Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
    Competing interests
    The authors declare that no competing interests exist.
  6. Rebecca Konietzny

    TDI Mass Spectrometry Laboratory, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Benedikt M Kessler

    TDI Mass Spectrometry Laboratory, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Haruhiko Koseki

    Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8424-5854
  9. Robert J Klose

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    For correspondence
    rob.klose@bioch.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8726-7888

Funding

Wellcome (098024/Z/11/Z)

  • Robert J Klose

European Research Council (681440)

  • Robert J Klose

Lister Institute of Preventive Medicine

  • Robert J Klose

Japan Agency for Medical Research and Development

  • Haruhiko Koseki

Sir Henry Wellcome Postdoctoral Fellowship (110286/Z/15/Z)

  • Angelika Feldmann

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Joaquín M Espinosa, University of Colorado School of Medicine, United States

Publication history

  1. Received: March 29, 2018
  2. Accepted: May 26, 2018
  3. Accepted Manuscript published: May 29, 2018 (version 1)
  4. Version of Record published: June 12, 2018 (version 2)

Copyright

© 2018, Dimitrova 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. Emilia A Dimitrova
  2. Takashi Kondo
  3. Angelika Feldmann
  4. Manabu Nakayama
  5. Yoko Koseki
  6. Rebecca Konietzny
  7. Benedikt M Kessler
  8. Haruhiko Koseki
  9. Robert J Klose
(2018)
FBXL19 recruits CDK-Mediator to CpG islands of developmental genes priming them for activation during lineage commitment
eLife 7:e37084.
https://doi.org/10.7554/eLife.37084

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