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

Patrick Laurette (1) , Thomas Strub (1) , Dana Koludrovic (1) , Céline Keime (2, 1) , Stéphanie Le Gras (2, 1) , H Seberg , E van Otterloo , H Imrichova , R Siddaway , S Aerts , R Cornell , Gabrielle Mengus (2, 1) , Irwin Davidson (1, 2)

1 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
2 IGBMC - Institut de génétique et biologie moléculaire et cellulaire

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.

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

Domaines: Biochimie, Biologie Moléculaire

Patrick Laurette, Thomas Strub, Dana Koludrovic, Céline Keime, Stéphanie Le Gras, et al.. Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells. eLife, 2015, 4 (Art. n°e06857), ⟨10.7554/eLife.06857⟩. ⟨hal-04238122⟩