The microphthalmia-associated transcription factor requires SWI/SNF enzymes to activate melanocyte-specific genes
Department of Cell Biology
Animals; Base Sequence; Chromatin; Chromosomal Proteins, Non-Histone; DNA Primers; Flow Cytometry; Gene Amplification; *Gene Expression Regulation, Enzymologic; Humans; Melanocytes; Mice; Microphthalmia-Associated Transcription Factor; Promoter Regions (Genetics); Transcription Factors; *Transcription, Genetic
Cell Biology | Life Sciences | Medicine and Health Sciences
The microphthalmia transcription factor (Mitf) activates melanocyte-specific gene expression, is critical for survival and proliferation of melanocytes during development, and has been described as an oncogene in malignant melanoma. SWI/SNF complexes are ATP-dependent chromatin-remodeling enzymes that play a role in many developmental processes. To determine the requirement for SWI/SNF enzymes in melanocyte differentiation, we introduced Mitf into fibroblasts that inducibly express dominant negative versions of the SWI/SNF ATPases, Brahma or Brahma-related gene 1 (BRG1). These dominant negative SWI/SNF components have been shown to inhibit gene activation events that normally require SWI/SNF enzymes. We found that Mitf-mediated activation of a subset of endogenous melanocyte-specific genes required SWI/SNF enzymes but that cell-cycle regulation occurred independently of SWI/SNF function. Activation of tyrosinase-related protein 1, a melanocyte-specific gene, correlated with SWI/SNF-dependent changes in chromatin accessibility at the endogenous locus. Both BRG1 and Mitf could be localized to the tyrosinase-related protein 1 and tyrosinase promoters by chromatin immunoprecipitation, whereas immunofluorescence and immunoprecipitation experiments indicate that Mitf and BRG1 co-localized in the nucleus and physically interacted. Together these results suggest that Mitf can recruit SWI/SNF enzymes to melanocyte-specific promoters for the activation of gene expression via induced changes in chromatin structure at endogenous loci.
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Citation: J Biol Chem. 2006 Jul 21;281(29):20233-41. Epub 2006 Apr 28. Link to article on publisher's site