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Gpnmb is a melanoblast-expressed, MITF-dependent gene.
- Source :
-
Pigment cell & melanoma research [Pigment Cell Melanoma Res] 2009 Feb; Vol. 22 (1), pp. 99-110. Date of Electronic Publication: 2008 Nov 01. - Publication Year :
- 2009
-
Abstract
- Expression profile analysis clusters Gpnmb with known pigment genes, Tyrp1, Dct, and Si. During development, Gpnmb is expressed in a pattern similar to Mitf, Dct and Si with expression vastly reduced in Mitf mutant animals. Unlike Dct and Si, Gpnmb remains expressed in a discrete population of caudal melanoblasts in Sox10-deficient embryos. To understand the transcriptional regulation of Gpnmb we performed a whole genome annotation of 2,460,048 consensus MITF binding sites, and cross-referenced this with evolutionarily conserved genomic sequences at the GPNMB locus. One conserved element, GPNMB-MCS3, contained two MITF consensus sites, significantly increased luciferase activity in melanocytes and was sufficient to drive expression in melanoblasts in vivo. Deletion of the 5'-most MITF consensus site dramatically reduced enhancer activity indicating a significant role for this site in Gpnmb transcriptional regulation. Future analysis of the Gpnmb locus will provide insight into the transcriptional regulation of melanocytes, and Gpnmb expression can be used as a marker for analyzing melanocyte development and disease progression.
- Subjects :
- Animals
Antigens, Neoplasm physiology
Base Sequence
Binding Sites
Cyclin-Dependent Kinase Inhibitor p15 physiology
Cyclin-Dependent Kinase Inhibitor p16 physiology
Enhancer Elements, Genetic
Eye Proteins metabolism
Gene Expression Profiling
Gene Expression Regulation, Developmental
Humans
Intramolecular Oxidoreductases physiology
Luciferases metabolism
MART-1 Antigen
Melanocytes cytology
Membrane Glycoproteins metabolism
Membrane Glycoproteins physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Microphthalmia-Associated Transcription Factor metabolism
Molecular Sequence Data
NIH 3T3 Cells
Neoplasm Proteins physiology
Oligonucleotide Array Sequence Analysis
Oxidoreductases physiology
Pigmentation
SOXE Transcription Factors physiology
Sequence Homology, Nucleic Acid
Transcriptional Activation
Zebrafish
gp100 Melanoma Antigen
Eye Proteins genetics
Melanocytes metabolism
Membrane Glycoproteins genetics
Microphthalmia-Associated Transcription Factor genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1755-1471
- Volume :
- 22
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Pigment cell & melanoma research
- Publication Type :
- Academic Journal
- Accession number :
- 18983539
- Full Text :
- https://doi.org/10.1111/j.1755-148X.2008.00518.x