Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells
- Institut de Génétique et de Biologie Moléculaire et Cellulaire, France
- Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, France
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.
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Animal experimentation: Animal experiments were performed in compliance with National Animal Care Guidelines (European Commission directive 86/609/CEE; French decree no. 87-848).
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© 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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Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells
eLife 4:e06857.
https://doi.org/10.7554/eLife.06857
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