Identification of a melanocyte-specific, microphthalmia-associated transcription factor-dependent regulatory element in the intronic duplication causing hair greying and melanoma in horses.
| Autor: | Sundström E; Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden., Komisarczuk AZ, Jiang L, Golovko A, Navratilova P, Rinkwitz S, Becker TS, Andersson L |
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| Jazyk: | angličtina |
| Zdroj: | Pigment cell & melanoma research [Pigment Cell Melanoma Res] 2012 Jan; Vol. 25 (1), pp. 28-36. Date of Electronic Publication: 2011 Sep 21. |
| DOI: | 10.1111/j.1755-148X.2011.00902.x |
| Abstrakt: | Greying with age in horses is an autosomal dominant trait, characterized by hair greying, high incidence of melanoma and vitiligo-like depigmentation. Previous studies have revealed that the causative mutation for this phenotype is a 4.6-kb intronic duplication in STX17 (Syntaxin 17). By using reporter constructs in transgenic zebrafish, we show that a construct containing two copies of the duplicated sequence acts as a strong enhancer in neural crest cells and has subsequent melanophore-specific activity during zebrafish embryonic development whereas a single copy of the duplicated sequence acts as a weak enhancer, consistent with the phenotypic manifestation of the mutation in horses. We further used luciferase assays to investigate regulatory regions in the duplication, to reveal tissue-specific activities of these elements. One region upregulated the reporter gene expression in a melanocyte-specific manner and contained two microphthalmia-associated transcription factor (MITF) binding sites, essential for the activity. Microphthalmia-associated transcription factor regulates melanocyte development, and these binding sites are outstanding candidates for mediating the melanocyte-specific activity of the element. These results provide strong support for the causative nature of the duplication and constitute an explanation for the melanocyte-specific effects of the Grey allele. (© 2011 John Wiley & Sons A/S.) |
| Databáze: | MEDLINE |
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