Received: 5 February 2018 | Accepted: 7 November 2018 DOI: 10.1002/jcp.27840 ORIGINAL RESEARCH ARTICLE BAF60A mediates interactions between the microphthalmia- associated transcription factor and the BRG1‐containing SWI/SNF complex during melanocyte differentiation Shweta Aras 1,2 | Srinivas Vinod Saladi 1,3 | Tupa Basuroy 1 | Himangi G. Marathe 1,4 | Patrick Lorès 5 | Ivana L. de la Serna 1 1 Department of Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio 2 Department of Cancer Biology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, 3 Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts 4 Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 5 INSERM U1016, Institut Cochin/CNRS UMR8104/ Universite Paris Descartes, Faculte de Medecine Cochin, Paris, France Correspondence Ivana L. de la Serna, Department of Biochemistry and Cancer Biology, University of Toledo College of Medicine and Life Sciences, 3035 Arlington Ave, Toledo, OH 43614. Email: ivana.delaserna@utoledo.edu Funding information National Institute of Arthritis and Musculoskeletal and Skin Diseases, Grant/Award Number: R01(ARO59379); National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Grant/Award Number: R01(ARO59379); University of Toledo Bridge Funding Abstract SWI/SNF chromatin remodeling enzymes are multisubunit complexes that contain one of two catalytic subunits, BRG1 or BRM and 9–11 additional subunits called BRG1 or BRM‐associated factors (BAFs). BRG1 interacts with the microphthalmia‐ associated transcription factor (MITF) and is required for melanocyte development in vitro and in vivo. The subunits of SWI/SNF that mediate interactions between BRG1 and MITF have not been elucidated. Three mutually exclusive isoforms of a 60‐kDa subunit (BAF60A, B, or C) often facilitate interactions with transcription factors during lineage specification. We tested the hypothesis that a BAF60 subunit promotes interactions between MITF and the BRG1‐containing SWI/SNF complex. We found that MITF can physically interact with BAF60A, BAF60B, and BAF60C. The interaction between MITF and BAF60A required the basic helix‐loop‐helix domain of MITF. Recombinant BAF60A pulled down recombinant MITF, suggesting that the interaction can occur in the absence of other SWI/SNF subunits and other transcriptional regulators of the melanocyte lineage. Depletion of BAF60A in differentiating melanoblasts inhibited melanin synthesis and expression of MITF target genes. MITF promoted BAF60A recruitment to melanocyte‐specific promoters, and BAF60A was required to promote BRG1 recruitment and chromatin remodeling. Thus, BAF60A promotes interactions between MITF and the SWI/SNF complex and is required for melanocyte differentiation. KEYWORDS BAF60A, chromatin remodeling, melanocyte differentiation, microphthalmia‐associated transcription factor (MITF) 1 | INTRODUCTION Melanocytes are cells that synthesize melanin and populate the skin, hair follicles, heart, choroid of the eye, and inner ear (Steingrimsson, Copeland, & Jenkins, 2004). During embryonic development, the neural crest gives rise to precursors called melanoblasts, which then differentiate into melanocytes. Melanocytes in the basal layer of the epidermis protect the skin against the damaging effects of ultraviolet radiation by synthesizing and transferring melanosomes containing melanin to surrounding keratinocytes (Kadekaro et al., 2003). They can transform to melanoma, an aggressive skin cancer with a poor prognosis. Key transcription factors that regulate melanocyte specification, survival, proliferation, and differentiation also have critical functions in melanoma. The microphthalmia‐associated transcription factor (MITF) is the master regulator of melanocyte differentiation and considered a J Cell Physiol. 2018;234:11780–11791. wileyonlinelibrary.com/journal/jcp 11780 | © 2018 Wiley Periodicals, Inc.