Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells

Patrick Laurette; Thomas Strub; Dana Koludrovic; Céline Keime; Stéphanie Le Gras; Hannah Seberg; Eric Van Otterloo; Hana Imrichova; Robert Siddaway; Stein Aerts; Robert A Cornell; Gabrielle Mengus; Irwin Davidson

doi:10.7554/eLife.06857

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Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells

Journal article

Open access

Peer reviewed

Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells

Patrick Laurette, Thomas Strub, Dana Koludrovic, Céline Keime, Stéphanie Le Gras, Hannah Seberg, Eric Van Otterloo, Hana Imrichova, Robert Siddaway, Stein Aerts, …

eLife, Vol.4(4), pp.1-40

03/24/2015

DOI: 10.7554/eLife.06857

PMCID: PMC4407272

PMID: 25803486

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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.

Chromatin - metabolism

Cell Proliferation

Microphthalmia-Associated Transcription Factor - metabolism

Humans

Gene Expression Regulation, Neoplastic

Chromatin Assembly and Disassembly

Melanocytes - metabolism

Nuclear Proteins - metabolism

DNA Repair - genetics

Melanoma - pathology

Regulatory Sequences, Nucleic Acid - genetics

Protein Transport

Transcription Factors - metabolism

DNA Helicases - metabolism

Multiprotein Complexes - metabolism

Animals

Melanoma - genetics

Models, Biological

Cell Line, Tumor

DNA Replication - genetics

Protein Binding

Transcription, Genetic

Mice

Genome

Details

Title: Subtitle: Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells
Creators: Patrick Laurette - Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
Thomas Strub - Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
Dana Koludrovic - Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
Céline Keime - Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
Stéphanie Le Gras - Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
Hannah Seberg - University of Iowa College of Medicine, Iowa City, United States
Eric Van Otterloo - University of Iowa College of Medicine, Iowa City, United States
Hana Imrichova - Laboratory of Computational Biology, Center for Human Genetics, University of Leuven, Leuven, Belgium
Robert Siddaway - Arthur and Sonia Labatt Brain Tumor Research Centre, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, Canada
Stein Aerts - Laboratory of Computational Biology, Center for Human Genetics, University of Leuven, Leuven, Belgium
Robert A Cornell - University of Iowa College of Medicine, Iowa City, United States
Gabrielle Mengus - Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
Irwin Davidson - Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France
Resource Type: Journal article
Publication Details: eLife, Vol.4(4), pp.1-40
DOI: 10.7554/eLife.06857
PMID: 25803486
PMCID: PMC4407272
NLM abbreviation: Elife
ISSN: 2050-084X
eISSN: 2050-084X
Publisher: England
Grant note: AR062547 / NIAMS NIH HHS
Language: English
Date published: 03/24/2015
Academic Unit: Anatomy and Cell Biology; Craniofacial Anomalies Research Center; Dental Research; Periodontics
Record Identifier: 9984025421702771

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