Article

Genetics of pigment cells: Lessons from the tyrosinase gene family

ISREC (Swiss Institute for Experimental Cancer Research), National Center of Competence in Research Molecular Oncology, Epalinges, Switzerland.
Histology and histopathology (Impact Factor: 2.1). 06/2006; 21(5):567-78.
Source: PubMed

ABSTRACT

In mammals, the melanin pigment is produced in two cell types of distinct developmental origins. The melanocytes of the skin originate form the neural crest whereas the retinal pigment epithelium (RPE) of the eye originates from the optic cup. The genetic programs governing these two cell types are thus quite different but have evolved to allow the expression of pigment cell-specific genes such as the three members of the tyrosinase-related family. Tyrosinase, Tyrp1 and Dct promoters contain a motif termed E-box which is bound by the transcription factor Mitf. These E-boxes are also found in the promoters of the corresponding fish genes, thus highlighting the pivotal role of Mitf in pigment cell-specific gene regulation. Mitf, which displays cell type-specific isoforms, transactivates the promoters of the tyrosinase gene family in both pigment cell lineages. However, specific DNA motifs have been found in these promoters, and they correspond to binding sites for RPE-specific factors such as Otx2 or for melanocyte-specific factors such as Sox10 or Pax3. The regulation of pigment cell-specific expression is also controlled by genetic elements located outside of the promoter, such as the tyrosinase distal regulatory element located at -15 kb which acts as a melanocyte-specific enhancer but also protects from spreading of condensed chromatin. Thus, by using the tyrosinase gene family as a model, it is possible to define the transcription factor networks that govern pigment production in either melanocytes or RPE.

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    • "The members of the tyrosinase-related family (tyrosinase and tyrosinase-related proteins TRP-1 (DHICAoxidase) and TRP-2, DOPAchrome tautomerase (Del Marmol and Beermann 1996) are also involved in the process of melanogenesis leading to the production of either eumelanin (brown-black) or pheomelanin (yellow-red). This difference in colour development in cell-specific pigment is regulated by MITF through transactivation of the promoters of the tyrosinase gene family (Murisier and Beermann 2006). The overall production of melanin is orchestrated by the pituitary through secretion of melanocyte-stimulating hormone and other cleavage products of a large precursor peptide proopiomelanocortin (Pritchard et al. 2002). "
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    • "Contrary, animals not exposed to light are often colorless, such as cavefish and nematodes (Singh and Nüsslein Volhard, 2015). Three members of the tyrosinase-related family (tyrosinase, tyrosinase-related protein-1 (Tyrp1), and dopachrome tautomerase (dct or Tyrp2)) are involved in melanogenesis, leading to the production of either eumelanin (brownblack ) or pheomelanin (yellow-red), which are both derived from L-tyrosine (Murisier and Beermann, 2006; Krauss et al., 2014). The synthesis of both melanin forms occurs within unique melanocyte organelles -the melanosomes. "
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    • "Ultraviolet radiation triggers the activation of p53 gene through DNA damage in the nucleus of keratinocytes (Lin and Fisher, 2007).This increases the modulation of gene encoding the propiomelanocortin (POMC) (Abdel et al., 2001). Posttranscriptional modification of POMC stimulates the production of melanocyte stimulating hormone (MSH) and β-endorphin (Biossy, 1988 and Rouzand et al., 2005).MSH is transported to the melanocytes where it binds to the melanocortin 1 receptor (MCR1) which activates cAMP response element binding protein (CREB) through downstream stimulation of cAMP (Storm and Elder, 2006 and Murisier and Beermann, 2006). The melanocyte master regulator MITF is activated further channelizing the transcription and modification of melanogenic enzymes with tyrosinase, thereby inducing the production of melanin pigment which is actively transported from the melanocytes in the dermis to the keratinocytes located in the epidermis where the pigment vesicles accumulate over the photo exposed surface of the nucleus subsequently causing tanning as a consequence (Thody and Graham, 1998). "
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