Title
The microphthalmia-associated transcription factor requires SWI/SNF enzymes to activate melanocyte-specific genes
UMMS Affiliation
Department of Cell Biology
Publication Date
2006-05-02
Document Type
Article
Subjects
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
Disciplines
Cell Biology | Life Sciences | Medicine and Health Sciences
Abstract
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.
DOI of Published Version
10.1074/jbc.M512052200
Source
J Biol Chem. 2006 Jul 21;281(29):20233-41. Epub 2006 Apr 28. Link to article on publisher's site
Journal/Book/Conference Title
The Journal of biological chemistry
Related Resources
PubMed ID
16648630
Repository Citation
de la Serna IL, Ohkawa Y, Higashi C, Dutta C, Osias J, Kommajosyula N, Tachibana T, Imbalzano AN. (2006). The microphthalmia-associated transcription factor requires SWI/SNF enzymes to activate melanocyte-specific genes. Open Access Articles. https://doi.org/10.1074/jbc.M512052200. Retrieved from https://escholarship.umassmed.edu/oapubs/680