Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells
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 trans...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/06857 |
| _version_ | 1818018528350961664 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Patrick Laurette |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:40:40Z |
| format | Article |
| id | doaj.art-b685e02106604747b3e01f01e7b91f35 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:40:40Z |
| publishDate | 2015-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-b685e02106604747b3e01f01e7b91f352022-12-22T02:05:30ZengeLife Sciences Publications LtdeLife2050-084X2015-03-01410.7554/eLife.06857Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cellsPatrick Laurette0Thomas Strub1Dana Koludrovic2Céline Keime3Stéphanie Le Gras4Hannah Seberg5Eric Van Otterloo6Hana Imrichova7Robert Siddaway8Stein Aerts9Robert A Cornell10Gabrielle Mengus11Irwin Davidson12Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, FranceDepartment of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, United StatesDepartment of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, FranceDepartment of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, FranceDepartment of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, FranceUniversity of Iowa College of Medicine, Iowa City, United StatesUniversity of Iowa College of Medicine, Iowa City, United StatesLaboratory of Computational Biology, Center for Human Genetics, University of Leuven, Leuven, BelgiumArthur and Sonia Labatt Brain Tumor Research Centre, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, CanadaLaboratory of Computational Biology, Center for Human Genetics, University of Leuven, Leuven, BelgiumUniversity of Iowa College of Medicine, Iowa City, United StatesDepartment of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, FranceDepartment of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, FranceMicrophthalmia-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.https://elifesciences.org/articles/06857chromatin remodellingSOX10CHD7YY1TFAP2Aenhancer |
| spellingShingle | 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 Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells eLife chromatin remodelling SOX10 CHD7 YY1 TFAP2A enhancer |
| title | Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells |
| title_full | Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells |
| title_fullStr | Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells |
| title_full_unstemmed | Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells |
| title_short | Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells |
| title_sort | transcription factor mitf and remodeller brg1 define chromatin organisation at regulatory elements in melanoma cells |
| topic | chromatin remodelling SOX10 CHD7 YY1 TFAP2A enhancer |
| url | https://elifesciences.org/articles/06857 |
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