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BRG1 interacts with SOX10 to establish the melanocyte lineage and to promote differentiation
- Source :
- Nucleic Acids Research
- Publication Year :
- 2017
- Publisher :
- Oxford University Press (OUP), 2017.
-
Abstract
- Mutations in SOX10 cause neurocristopathies which display varying degrees of hypopigmentation. Using a sensitized mutagenesis screen, we identified Smarca4 as a modifier gene that exacerbates the phenotypic severity of Sox10 haplo-insufficient mice. Conditional deletion of Smarca4 in SOX10 expressing cells resulted in reduced numbers of cranial and ventral trunk melanoblasts. To define the requirement for the Smarca4 -encoded BRG1 subunit of the SWI/SNF chromatin remodeling complex, we employed in vitro models of melanocyte differentiation in which induction of melanocyte-specific gene expression is closely linked to chromatin alterations. We found that BRG1 was required for expression of Dct, Tyrp1 and Tyr, genes that are regulated by SOX10 and MITF and for chromatin remodeling at distal and proximal regulatory sites. SOX10 was found to physically interact with BRG1 in differentiating melanocytes and binding of SOX10 to the Tyrp1 distal enhancer temporally coincided with recruitment of BRG1. Our data show that SOX10 cooperates with MITF to facilitate BRG1 binding to distal enhancers of melanocyte-specific genes. Thus, BRG1 is a SOX10 co-activator, required to establish the melanocyte lineage and promote expression of genes important for melanocyte function.
- Subjects :
- 0301 basic medicine
Cellular differentiation
SOX10
Gene Expression
Mice, Transgenic
Biology
Chromatin remodeling
Cell Line
03 medical and health sciences
Melanocyte differentiation
Genetics
Animals
Enhancer
Melanins
Regulation of gene expression
Mice, Inbred BALB C
Membrane Glycoproteins
SOXE Transcription Factors
Gene regulation, Chromatin and Epigenetics
DNA Helicases
Nuclear Proteins
Cell Differentiation
Molecular biology
Chromatin
Mice, Inbred C57BL
Enhancer Elements, Genetic
030104 developmental biology
Gene Expression Regulation
embryonic structures
SMARCA4
Melanocytes
Oxidoreductases
Transcription Factors
Subjects
Details
- ISSN :
- 13624962 and 03051048
- Volume :
- 45
- Database :
- OpenAIRE
- Journal :
- Nucleic Acids Research
- Accession number :
- edsair.doi.dedup.....cc66e9aea86bc5d3e7fa101f3ba012c4