Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells.
Fiche publication
Date publication
mars 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DAVIDSON Irwin
Tous les auteurs :
Laurette P, Strub T, Koludrovic D, Keime C, Le Gras S, Seberg H, Van Otterloo E, Imrichova H, Siddaway R, Aerts S, Cornell RA, Mengus G, Davidson I
Lien Pubmed
Résumé
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.
Référence
Elife. 2015 Mar 24;4