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Gpnmb is a melanoblast-expressed, MITF-dependent gene

Loftus, SK; Antonellis, A; Matera, I; Renaud, G; Baxter, LL; Reid, D; Wolfsberg, TG; Chen, Y; Wang, C; NISC Comparative Sequencing Program, ; et al. Loftus, SK; Antonellis, A; Matera, I; Renaud, G; Baxter, LL; Reid, D; Wolfsberg, TG; Chen, Y; Wang, C; NISC Comparative Sequencing Program, ; Prasad, MK; Bessling, SL; McCallion, AS; Green, ED; Bennett, DC; Pavan, WJ (2009) Gpnmb is a melanoblast-expressed, MITF-dependent gene. PIGMENT CELL & MELANOMA RESEARCH, 22 (1). 99 - 110. ISSN 1755-1471 https://doi.org/10.1111/j.1755-148X.2008.00518.x
SGUL Authors: Bennett, Dorothy Catherine

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.

Item Type: Article
Additional Information: Copyright: 2008 No claim to original US government works, Journal Compilation Copyright: 2008 Blackwell Munksgaard
Keywords: Animals, Antigens, Neoplasm, Base Sequence, Binding Sites, Cyclin-Dependent Kinase Inhibitor p15, Cyclin-Dependent Kinase Inhibitor p16, Enhancer Elements, Genetic, Eye Proteins, Gene Expression Profiling, Gene Expression Regulation, Developmental, Humans, Intramolecular Oxidoreductases, Luciferases, MART-1 Antigen, Melanocytes, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Microphthalmia-Associated Transcription Factor, Molecular Sequence Data, NIH 3T3 Cells, Neoplasm Proteins, Oligonucleotide Array Sequence Analysis, Oxidoreductases, Pigmentation, SOXE Transcription Factors, Sequence Homology, Nucleic Acid, Transcriptional Activation, Zebrafish, gp100 Melanoma Antigen, Science & Technology, Life Sciences & Biomedicine, Oncology, Cell Biology, Dermatology, CELL BIOLOGY, DERMATOLOGY, ONCOLOGY, Gpnmb, Mitf, Sox10, melanoblast, melanocyte, melanoma, MELANOCYTE-SPECIFIC EXPRESSION, TRANSCRIPTION FACTOR, DOPACHROME-TAUTOMERASE, EMBRYONIC-DEVELOPMENT, WAARDENBURG-SYNDROME, MALIGNANT-MELANOMA, MOUSE MELANOCYTES, SOX10 MUTATION, DBA/2J MICE, MICROPHTHALMIA, 11 Medical And Health Sciences, 06 Biological Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS)
Journal or Publication Title: PIGMENT CELL & MELANOMA RESEARCH
ISSN: 1755-1471
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Dates:
DateEvent
1 February 2009Published
Web of Science ID: WOS:000262513500014
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URI: http://openaccess.sgul.ac.uk/id/eprint/100945
Publisher's version: https://doi.org/10.1111/j.1755-148X.2008.00518.x

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