1. Biochemistry and Chemical Biology
  2. Chromosomes and Gene Expression
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Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells

  1. Patrick Laurette
  2. Thomas Strub
  3. Dana Koludrovic
  4. Céline Keime
  5. Stéphanie Le Gras
  6. Hannah Seberg
  7. Eric Van Otterloo
  8. Hana Imrichova
  9. Robert Siddaway
  10. Stein Aerts
  11. Robert A Cornell
  12. Gabrielle Mengus
  13. Irwin Davidson  Is a corresponding author
  1. Institut de Génétique et de Biologie Moléculaire et Cellulaire, France
  2. Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, France
Research Article
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Cite this article as: eLife 2015;4:e06857 doi: 10.7554/eLife.06857

Abstract

Microphthalmia-associated transcription factor (MITF) is the master regulator of the melanocyte lineage. To understand how MITF regulates transcription, we used tandem affinity purification and mass spectrometry to define a comprehensive MITF interactome identifying novel cofactors involved in transcription, DNA replication and repair and chromatin organisation. We show that MITF interacts with a PBAF chromatin remodelling complex comprising BRG1 and CHD7. BRG1 is essential for melanoma cell proliferation in vitro and for normal melanocyte development in vivo. MITF and SOX10 actively recruit BRG1 to a set of MITF-associated regulatory elements (MAREs) at active enhancers. Combinations of MITF, SOX10, TFAP2A and YY1 bind between two BRG1-occupied nucleosomes thus defining both a signature of transcription factors essential for the melanocyte lineage and a specific chromatin organisation of the regulatory elements they occupy. BRG1 also regulates the dynamics of MITF genomic occupancy. MITF-BRG1 interplay thus plays an essential role in transcription regulation in melanoma.

Article and author information

Author details

  1. Patrick Laurette

    Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
    Competing interests
    No competing interests declared.
  2. Thomas Strub

    Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
    Competing interests
    No competing interests declared.
  3. Dana Koludrovic

    Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
    Competing interests
    No competing interests declared.
  4. Céline Keime

    Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
    Competing interests
    No competing interests declared.
  5. Stéphanie Le Gras

    Department of Functional Genomics and Cancer, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, Strasbourg, France
    Competing interests
    No competing interests declared.
  6. Hannah Seberg

    Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
    Competing interests
    No competing interests declared.
  7. Eric Van Otterloo

    Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
    Competing interests
    No competing interests declared.
  8. Hana Imrichova

    Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
    Competing interests
    No competing interests declared.
  9. Robert Siddaway

    Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
    Competing interests
    No competing interests declared.
  10. Stein Aerts

    Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
    Competing interests
    No competing interests declared.
  11. Robert A Cornell

    Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
    Competing interests
    No competing interests declared.
  12. Gabrielle Mengus

    Department of Functional Genomics and Cancer, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, Strasbourg, France
    Competing interests
    No competing interests declared.
  13. Irwin Davidson

    Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
    For correspondence
    irwin@igbmc.fr
    Competing interests
    Irwin Davidson, Reviewing editor, eLife.

Ethics

Animal experimentation: Animal experiments were performed in compliance with National Animal Care Guidelines (European Commission directive 86/609/CEE; French decree no. 87-848).

Reviewing Editor

  1. Michael R Green, Howard Hughes Medical Institute, University of Massachusetts Medical School, United States

Publication history

  1. Received: February 6, 2015
  2. Accepted: March 24, 2015
  3. Accepted Manuscript published: March 24, 2015 (version 1)
  4. Version of Record published: April 23, 2015 (version 2)

Copyright

© 2015, Laurette 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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