BRG1 interacts with SOX10 to establish the melanocyte lineage and to promote differentiation.

Marathe HG, Watkins-Chow DE, Weider M, Hoffmann A, Trivedi A, Aras S, Mehta G, Basuroy T, Mehrotra A, Bennett DC, Wegner M, Pavan WJ, De La Serna IL (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Nucleic Acids Research Oxford University Press

Publisher: Oxford University Press

Book Volume: 45

Pages Range: 6442-6458

Journal Issue: 45

DOI: 10.1093/nar/gkx259

Abstract

Mutations in SOX10 cause neurocristopathies which display varying degrees of hypopigmentation. Using a sensitized mutagenesis screen, we identified Smarca4 as a modifier gene that exacerbates the phenotypic severity ofSox10 haplo-insufficientmice. Conditional deletion of Smarca4 in SOX10 expressing cells resulted in reduced numbers of cranial and ventral trunk melanoblasts. To define the requirement for the Smarca4 -encoded BRG1 subunit of the SWI/SNF chromatin remodeling complex, we employed in vitro models of melanocyte differentiation in which induction of melanocyte-specific gene expression is closely linked to chromatin alterations. We found that BRG1 was required for expression of Dct, Tyrp1 and Tyr, genes that are regulated by SOX10 and MITF and for chromatin remodeling at distal and proximal regulatory sites. SOX10 was found to physically interact with BRG1 in differentiating melanocytes and binding of SOX10 to the Tyrp1 distal enhancer temporally coincided with recruitment of BRG1. Our data show that SOX10 cooperates with MITF to facilitate BRG1 binding to distal enhancers of melanocyte-specific genes. Thus, BRG1 is a SOX10 co-activator, required to establish the melanocyte lineage and promote expression of genes important for melanocyte function.

Authors with CRIS profile

Matthias Weider Lehrstuhl für Biochemie und Pathobiochemie Alana Hoffmann Lehrstuhl für Biochemie und Pathobiochemie Michael Wegner Lehrstuhl für Biochemie und Pathobiochemie

Additional Organisation(s)

Emil-Fischer-Zentrum (Emil Fischer Center)

Involved external institutions

University of Toledo US United States (USA) (US) National Human Genome Research Institute (NHGRI) US United States (USA) (US) St George's, University of London (SGUL) / St George's Hospital Medical School GB United Kingdom (GB)

How to cite

APA:

Marathe, H.G., Watkins-Chow, D.E., Weider, M., Hoffmann, A., Trivedi, A., Aras, S.,... De La Serna, I.L. (2017). BRG1 interacts with SOX10 to establish the melanocyte lineage and to promote differentiation. Nucleic Acids Research, 45(45), 6442-6458. https://doi.org/10.1093/nar/gkx259

MLA:

Marathe, Himangi G., et al. "BRG1 interacts with SOX10 to establish the melanocyte lineage and to promote differentiation." Nucleic Acids Research 45.45 (2017): 6442-6458.

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