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• W2045937114 abstract "The microphthalmia-associated transcription factor (MITF) promotes melanocyte differentiation and cell-cycle arrest. Paradoxically, MITF also promotes melanoma survival and proliferation, acting like a lineage survival oncogene. Thus, it is critically important to understand the mechanisms that regulate MITF activity in melanoma cells. SWI/SNF chromatin remodeling enzymes are multiprotein complexes composed of one of two related ATPases, BRG1 or BRM, and 9-12-associated factors (BAFs). We previously determined that BRG1 interacts with MITF to promote melanocyte differentiation. However, it was unclear whether SWI/SNF enzymes regulate the expression of different classes of MITF target genes in melanoma. In this study, we characterized SWI/SNF subunit expression in melanoma cells and observed downregulation of BRG1 or BRM, but not concomitant loss of both ATPases. Re-introduction of BRG1 in BRG1-deficient SK-MEL5 cells enhanced expression of differentiation-specific MITF target genes and resistance to cisplatin. Downregulation of the single ATPase, BRM, in SK-MEL5 cells inhibited expression of both differentiation-specific and pro-proliferative MITF target genes and inhibited tumorigenicity in vitro. Our data suggest that heterogeneous SWI/SNF complexes composed of either the BRG1 or BRM subunit promote expression of distinct and overlapping MITF target genes and that at least one ATPase is required for melanoma tumorigenicity." @default.
• W2045937114 created "2016-06-24" @default.
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• W2045937114 date "2009-09-28" @default.
• W2045937114 modified "2023-10-17" @default.
• W2045937114 title "Heterogeneous SWI/SNF chromatin remodeling complexes promote expression of microphthalmia-associated transcription factor target genes in melanoma" @default.
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• W2045937114 doi "https://doi.org/10.1038/onc.2009.304" @default.
• W2045937114 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2803337" @default.
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