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


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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    • "Other cells if the necessary enzymes are present will also produce melanins, e.g. epithelia of the retina and iris, some neurones and adipocytes (Ito and Wakamatsu 2008; Murisier and Beermann 2006). "
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    ABSTRACT: The pigments found in plants, animals and humic substances are well described and classified. In humans considerable progress has been made with the main pigment melanin in defining its biochemistry, the different types and function. However, analytical techniques to show these differences in vivo are still not readily available. NMR and IR spectroscopy are relatively insensitive and reveal only major structural differences. Techniques utilising MS are useful in determining elemental content but require further studies to optimise conditions for accurate mass analysis. How the components may be structurally organised seems to be the most problematic with scanning TEM and the improved FTIR of use in this respect. As regards understanding the nature of the pigment related to HGA seen in patients with Alkaptonuria (AKU), it is still thought of as a melaninlike pigment simply because of its colour and likewise thought to be a polymer of undetermined size. It is important that detailed analysis be carried out to define more accurately this pigment. However, observations suggest it to be the same as the HGA-derived pigment, pyomelanin, produced by bacteria and containing both quinone and phenolic groups. The interesting developments in alkaptonuria will be to understand how such a polymer can cause such profound collagen and connective tissue damage and how best to reverse this process.
    06/2015; DOI:10.1007/8904_2015_453
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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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    ABSTRACT: Human phenotype including skin colour patterns is associated with genetic, evolutional as well as cultural aspects which rely on production of melanin. Melasma is crucial disorder related to the skin that affects the population. The aim of this study was to evaluate the various contributing circulating biochemical markers that could be responsible for melasma. Fifty (50) patients suffering from melasma and twenty (20) clinically healthy individuals were selected for this study. Lipid profile as well as oxidative and anti-oxidative profiles was estimated in patients and healthy individuals. HDL was decreased in patients (1.39±0.10∗) as compared to control (1.73±0.17) group. On contrary, TCh (5.48±0.92∗), Tg (2.59±0.53∗), and LDL (2.48±0.23∗) were raised in patients. Alterations in lipid profile were statistically significant (P<0.05). Malondialdehyde (MDA) was elevated (5.44±1.14∗) in patients while anti-oxidative parameters were decreased in patients and all were statistically significant (P<0.05). It can be concluded that not only the melanin but also other circulating biomarkers like cholesterol, Tg, HDL and LDL may be the contributing factors for the progression of melasma. Moreover, oxidative stress markers may also be used in disease prognosis and diagnosis.
    Pakistan Journal of Medical and Health Sciences 01/2015; 9(1):275-277.
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    • "P = 1.75×10-16), and Sox10 (0.67; P = 5.29×10-3). Estrogen-related receptor gamma a (Esrrga) was the gene with highest fold change in yellow samples, Tyrosinase (Tyr) is a rate-limiting biosynthetic enzyme of melanin, and the transcription factors Pax3 and Sox10 are important in the differentiation of melanocytes [11, 23]. In all four cases, the direction of change was consistent between the two methods (Figure 2). "
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    ABSTRACT: Background The annual fish Nothobranchius furzeri is characterized by a natural dichromatism with yellow-tailed and red-tailed male individuals. These differences are due to different distributions of xanthophores and erythrophores in the two morphs. Previous crossing studies have showed that dichromatism in N. furzeri is inherited as a simple Mendelian trait with the yellow morph dominant over the red morph. The causative genetic variation was mapped by linkage analysis in a chromosome region containing the Mc1r locus. However, subsequent mapping showed that Mc1r is most likely not responsible for the color difference in N. furzeri. To gain further insight into the molecular basis of this phenotype, we performed RNA-seq on F2 progeny of a cross between N. furzeri male and N. kadleci female. Results We identified 210 differentially-expressed genes between yellow and red fin samples. Functional annotation analysis revealed that genes with higher transcript levels in the yellow morph are enriched for the melanin synthesis pathway indicating that xanthophores are more similar to melanophores than are the erythrophores. Genes with higher expression levels in red-tails included xanthine dehydrogenase (Xdh), coding for a biosynthetic enzyme in the pteridine synthesis pathway, and genes related to muscle contraction. Comparison of DEGs obtained in this study with genes associated with pigmentation in the Midas cichlid (A. citrinellus) reveal similarities like involvement of the melanin biosynthesis pathway, the genes Ptgir, Rasef (RAS and EF-hand domain containing), as well as genes primarily expressed in muscle such as Ttn and Ttnb (titin, titin b). Conclusions Regulation of genes in the melanin synthetic pathway is an expected finding and shows that N. furzeri is a genetically-tractable species for studying the genetic basis of natural phenotypic variations. The current list of differentially-expressed genes can be compared with the results of fine-mapping, to reveal the genetic architecture of this natural phenotype. However, an evolutionarily-conserved role of muscle-related genes in tail fin pigmentation is novel finding and interesting perspective for the future. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-754) contains supplementary material, which is available to authorized users.
    BMC Genomics 09/2014; 15(1):754. DOI:10.1186/1471-2164-15-754 · 3.99 Impact Factor
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