Gpnmb is a melanoblast-expressed, MITF-dependent gene

Stacie K. Loftus; Anthony Antonellis; Ivana Matera; Gabriel Renaud; Laura L. Baxter; Duncan Reid; Tyra G. Wolfsberg; Yidong Chen; Chenwei Wang; Megana K. Prasad; Seneca L. Bessling; Andrew S. McCallion; Eric D. Green; Dorothy C. Bennett; William J. Pavan

doi:10.1111/j.1755-148X.2008.00518.x

Gpnmb is a melanoblast-expressed, MITF-dependent gene

Stacie K. Loftus, Anthony Antonellis, Ivana Matera, Gabriel Renaud, Laura L. Baxter, Duncan Reid, Tyra G. Wolfsberg, Yidong Chen, Chenwei Wang, Megana K. Prasad, Seneca L. Bessling, Andrew S. McCallion, Eric D. Green, Dorothy C. Bennett, William J. Pavan

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

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.

Original language	English (US)
Pages (from-to)	99-110
Number of pages	12
Journal	Pigment Cell and Melanoma Research
Volume	22
Issue number	1
DOIs	https://doi.org/10.1111/j.1755-148X.2008.00518.x
State	Published - Feb 2009

Keywords

Gpnmb
Melanoblast
Melanocyte
Melanoma
Mitf
Sox10

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Oncology
Dermatology

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Loftus, S. K., Antonellis, A., Matera, I., Renaud, G., Baxter, L. L., Reid, D., Wolfsberg, T. G., Chen, Y., Wang, C., Prasad, M. K., Bessling, S. L., McCallion, A. S., Green, E. D., Bennett, D. C., & Pavan, W. J. (2009). Gpnmb is a melanoblast-expressed, MITF-dependent gene. Pigment Cell and Melanoma Research, 22(1), 99-110. https://doi.org/10.1111/j.1755-148X.2008.00518.x

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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.",

keywords = "Gpnmb, Melanoblast, Melanocyte, Melanoma, Mitf, Sox10",

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AU - Renaud, Gabriel

AU - Baxter, Laura L.

AU - Reid, Duncan

AU - Wolfsberg, Tyra G.

AU - Chen, Yidong

AU - Wang, Chenwei

AU - Prasad, Megana K.

AU - Bessling, Seneca L.

AU - McCallion, Andrew S.

AU - Green, Eric D.

AU - Bennett, Dorothy C.

AU - Pavan, William J.

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N2 - 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.

AB - 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.

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KW - Melanoma

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Gpnmb is a melanoblast-expressed, MITF-dependent gene

Abstract

Keywords

ASJC Scopus subject areas

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