title: Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells.
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.
authors: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France.
authors: Patrick
authors: P
authors: Laurette
authors: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France.
authors: Thomas
authors: T
authors: Strub
authors: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France.
authors: Dana
authors: D
authors: Koludrovic
authors: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France.
authors: Céline
authors: C
authors: Keime
authors: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France.
authors: Stéphanie
authors: S
authors: Le Gras
authors: University of Iowa College of Medicine, Iowa City, United States.
authors: Hannah
authors: H
authors: Seberg
authors: University of Iowa College of Medicine, Iowa City, United States.
authors: Eric
authors: E
authors: Van Otterloo
authors: Laboratory of Computational Biology, Center for Human Genetics, University of Leuven, Leuven, Belgium.
authors: Hana
authors: H
authors: Imrichova
authors: Arthur and Sonia Labatt Brain Tumor Research Centre, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, Canada.
authors: Robert
authors: R
authors: Siddaway
authors: Laboratory of Computational Biology, Center for Human Genetics, University of Leuven, Leuven, Belgium.
authors: Stein
authors: S
authors: Aerts
authors: University of Iowa College of Medicine, Iowa City, United States.
authors: Robert A
authors: RA
authors: Cornell
authors: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France.
authors: Gabrielle
authors: G
authors: Mengus
authors: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France.
authors: Irwin
authors: I
authors: Davidson
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D006801:Humans; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D051739:Microphthalmia-Associated Transcription Factor; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D014157:Transcription Factors; C084108:SMARCA4 protein, human; C513194:Smarca4 protein, mouse; D004265:DNA Helicases
keywords: CHD7; SOX10; TFAP2A; YY1; biochemistry; chromatin remodelling; chromosomes; enhancer; genes; human; mouse