Analysis of the transcriptional regulation of melanocytic genes by alphaMSH using the cDNA microarray technique.
Studies of mammalian pigmentation have identified many genes involved in the development, migration, and function of melanocytes. Molecular and biochemical mechanisms that switch melanocytes between the production of eumelanin or pheomelanin involve the opposing action of two signaling molecules, alpha-Melanocyte Stimulating Hormone (alphaMSH) and Agouti Signal Protein (ASP). AlphaMSH affects various aspects of melanocyte behavior, stimulating melanocyte dendricity, attachment to extracellular matrix proteins, but also up-regulating the expression of eumelanogenic genes. In response to ASP, melanocytes switch from producing eumelanin to pheomelanin concomitant with the down-regulation of melanogenic genes transcription. Since activation of signaling pathways leads to mRNA expression, microarray technology can provide a quantitative assessment of the consequences of this activation. Significant up/down regulation of all known melanogenic genes by alphaMSH/ASP in cultured melanocytes has been previously reported. We have now used the cDNA microarray technique to screen alphaMSH-treated melanocytes to identify genes that are transcriptionally enhanced by this factor. We report the melanocytic expression and alphaMSH up-regulation of 11 genes spanning 7 functional categories such as apoptosis, body weight control, intracellular transport, signal transduction, oncogenic transformation, transcription factors and genes coding for keratin associated proteins.
Rouzaud
F
F
Laboratory of Cell Biology, National Institutes of Health, National Cancer Institute, Bethesda, MD 20892, USA.
Hearing
V J
VJ
D054366:Agouti Signaling Protein; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001692:Biological Transport / Q000235:genetics / Q000502:physiology; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D007633:Keratins / Q000235:genetics / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects* / Q000235:genetics; D000521:alpha-MSH / Q000494:pharmacology*
D054366:Agouti Signaling Protein; D036341:Intercellular Signaling Peptides and Proteins; D008543:Melanins; D014157:Transcription Factors; C018362:pheomelanin; C041877:eumelanin; D000521:alpha-MSH; D007633:Keratins