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Melanin\u2010producing melanocytes maintain a gene expression program ensuring appropriate enzymatic conversion of metabolites into the pigment, melanin, and transfer to surrounding cells. During neuroectodermal development, SMARCA4 (BRG1), the catalytic subunit of SWItch\/Sucrose Non\u2010Fermentable (SWI\/SNF) chromatin remodeling complexes, is essential for lineage specification. SMARCA4 is also required for development of multipotent neural crest precursors into melanoblasts, which differentiate into pigment\u2010producing melanocytes. In addition to the catalytic domain, SMARCA4 and several SWI\/SNF subunits contain bromodomains which are amenable to pharmacological inhibition. We investigated the effects of pharmacological inhibitors of SWI\/SNF bromodomains on melanocyte differentiation. Strikingly, treatment of murine melanoblasts and human neonatal epidermal melanocytes with selected bromodomain inhibitors abrogated melanin synthesis and visible pigmentation. Using functional genomics, iBRD9, a small molecule selective for the bromodomain of BRD9 was found to repress pigmentation\u2010specific gene expression. Depletion of BRD9 confirmed a requirement for expression of pigmentation genes in the differentiation program from melanoblasts into pigmented melanocytes and in melanoma cells. Chromatin immunoprecipitation assays showed that iBRD9 disrupts the occupancy of BRD9 and the catalytic subunit SMARCA4 at melanocyte\u2010specific loci. These data indicate that BRD9 promotes melanocyte pigmentation whereas pharmacological inhibition of BRD9 is repressive.<\/jats:p>","DOI":"10.1111\/pcmr.13068","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T14:25:18Z","timestamp":1663338318000},"page":"19-32","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Epigenetic and pharmacological control of pigmentation via Bromodomain Protein 9 (<scp>BRD9<\/scp>)"],"prefix":"10.1111","volume":"36","author":[{"given":"Tupa","family":"Basuroy","sequence":"first","affiliation":[{"name":"Department of Cell and Cancer Biology University of Toledo College of Medicine and Life Sciences  Toledo Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Dreier","sequence":"additional","affiliation":[{"name":"Department of Cell and Cancer Biology University of Toledo College of Medicine and Life Sciences  Toledo Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caitlin","family":"Baum","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Toledo College of Medicine and Life Sciences  Toledo Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Blomquist","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Toledo College of Medicine and Life Sciences  Toledo Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Trumbly","sequence":"additional","affiliation":[{"name":"Department of Cell and Cancer Biology University of Toledo College of Medicine and Life Sciences  Toledo Ohio USA"},{"name":"Department of Medical Education University of Toledo College of Medicine and Life Sciences  Toledo Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabian 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