The transcription factor TBX2 regulates melanogenesis in melanocytes by repressing Oca2
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The T-box transcription factor TBX2 is known for its role as a critical regulator of melanoma cell proliferation, but its role in regulating melanogenesis has not been widely studied. Here we use a series of experiments to show in primary and immortalized mouse melanocytes that TBX2 acts as regulator of melanogenesis by repressing the expression of the gene encoding the melanosomal protein OCA2. We find that α-MSH or forskolin, both of which stimulate melanogenesis, also reduce TBX2 expression, and that specific knockdown of TBX2 increases melanogenesis. This effect primarily involves an increase in Oca2 expression as the combined knockdown of both Tbx2 and Oca2 interferes with the Tbx2 knockdown-mediated increase in melanogenesis. Standard chromatin immunoprecipitation and reporter assays suggest that TBX2 represses Oca2 at least in part directly. Hence, the results suggest that TBX2 may act as a nexus linking cell proliferation and melanogenesis.
KeywordsT-box transcription factor Transcriptional regulation Pigmentary disease Melanocyte Pigmentation
We thank Dr. Dorothy Bennett for reagents, and Dr. Heinz Arnheiter for thoughtful comments on the manuscript. This work was supported by the National Natural Science Foundation of China (81570892, 31201031), the Natural Science Foundation of Zhejiang Province (LQ16C070001, LQ13H120004,LQ13H120004,LY13C090004), and the Research Grant of Wenzhou Medical University.
- 12.Bellono NW, Escobar IE, Lefkovith AJ, Marks MS, Oancea E (2014) An intracellular anion channel critical for pigmentation. Elife 16:e04543Google Scholar
- 24.Ismland F, McGowan K, Rubin CJ, Henegar C, Sundström E, Berglund J, Schwochow D, Gustafson U, Imsland P, Lindblad-Toh K, Lindgren G, Mikko S, Millon L, Wade C, Schubert M, Orlando L, Penedo MC, Barsh GS, Andersson L (2016) Regulatory mutations in TBX3 disrupt asymmetric hair pigmentation that underlies Dun camouflage color in horses. Nat Genet 48(2):152–158CrossRefGoogle Scholar