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Elife. 2015 Mar 24;4. doi: 10.7554/eLife.06857.

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

Author information

1
Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg, France.
2
University of Iowa College of Medicine, Iowa City, United States.
3
Laboratory of Computational Biology, Center for Human Genetics, University of Leuven, Leuven, Belgium.
4
Arthur and Sonia Labatt Brain Tumor Research Centre, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, Canada.

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.

KEYWORDS:

CHD7; SOX10; TFAP2A; YY1; biochemistry; chromatin remodelling; chromosomes; enhancer; genes; human; mouse

PMID:
25803486
PMCID:
PMC4407272
DOI:
10.7554/eLife.06857
[Indexed for MEDLINE]
Free PMC Article

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