Delineating the role of MITF isoforms in pigmentation and tissue homeostasis
| Autor: | Elyse K. Paterson‐Coleman, Jonathan Neumann, Eric Pearlman, Michaela E. Marshall, Grant R. MacGregor, Anand K. Ganesan, Jessica L. Flesher, Priya Vasudeva, Rolando Ruiz-Vega |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Gene isoform Mice Transgenic Dermatology Biology Eye Article General Biochemistry Genetics and Molecular Biology Melanin Retinoids 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Animals Homeostasis Humans Protein Isoforms Iris pigment epithelium Promoter Regions Genetic Enhancer Tissue homeostasis Microphthalmia-Associated Transcription Factor Binding Sites Retinal pigment epithelium integumentary system Pigmentation Waardenburg syndrome Retinoic Acid Receptor alpha medicine.disease Microphthalmia-associated transcription factor Cell biology Mice Inbred C57BL body regions HEK293 Cells Phenotype 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Melanocytes sense organs Protein Binding |
| Zdroj: | Pigment Cell Melanoma Res |
| ISSN: | 1755-148X 1755-1471 |
| DOI: | 10.1111/pcmr.12828 |
| Popis: | MITF, a gene that is mutated in familial melanoma and Waardenburg syndrome, encodes multiple isoforms expressed from alternative promoters that share common coding exons but have unique amino termini. It is not completely understood how these isoforms influence pigmentation in different tissues and how the expression of these independent isoforms of MITF is regulated. Here, we show that melanocytes express two isoforms of MITF, MITF-A and MITF-M. The expression of MITF-A is partially regulated by a newly identified retinoid enhancer element located upstream of the MITF-A promoter. Mitf-A knockout mice have only subtle changes in melanin accumulation in the hair and reduced Tyr expression in the eye. In contrast, Mitf-M-null mice have enlarged kidneys, lack neural crest-derived melanocytes in the skin, choroid, and iris stroma, yet maintain pigmentation within the retinal pigment epithelium and iris pigment epithelium of the eye. Taken together, these studies identify a critical role for MITF-M in melanocytes, a minor role for MITF-A in regulating pigmentation in the hair and Tyr expression in the eye, and a novel role for MITF-M in size control of the kidney. |
| Databáze: | OpenAIRE |
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