Molecular and Cellular Biochemistry

, Volume 415, Issue 1–2, pp 103–109 | Cite as

The transcription factor TBX2 regulates melanogenesis in melanocytes by repressing Oca2

  • Yu Chen
  • Li Pan
  • Zhongyuan Su
  • Jing Wang
  • Huirong Li
  • Xiaoyin Ma
  • Yin Liu
  • Fan Lu
  • Jia Qu
  • Ling HouEmail author


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.


T-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.

Supplementary material

11010_2016_2680_MOESM1_ESM.jpg (861 kb)
Figure S1. α-MSH or forskolin promotes melanogenesis in primary melanocytes. After treatment with 100 nM α-MSH or 5μM forskolin for three days, we took bright-field images of primary melanocytes (A) and analyzed melanin content (B). Black arrows indicate heavily pigmented melanocytes. (C) After treatment with 100nM α-MSH or 5μM forskolin for two days, the expression levels of several melanogenesis-associated genes were examined by relative real-time PCR. Note that in primary melanocytes, the expression of Tbx2 was downregulated after treatment with α-MSH or 5μM forskolin. Experiments were done in triplicates and error bars were represented as mean ±SD. * indicates P < 0.05, ** indicates P < 0.01, and *** indicates P < 0.001. Scale bar is 50 μm. Supplementary material 1 (JPEG 861 kb)
11010_2016_2680_MOESM2_ESM.jpg (1.2 mb)
Figure S2. Knockdown of Tbx2 promotes melanogenesis in primary melanocytes and melan-a cells. (A-B) 4 days after transfection with si-C, si-Tbx2-1 or si-Tbx2-2, bright-field images of primary melanocytes were recorded (A) and melanin content was analyzed (B). (C-E) Four days after transfection with si-C, si-Tbx2-1 or si-Tbx2-2, transmitted bright-field images of melan-a cells were recorded (C), pellets of melan-a cells were collected (D), and melanin content was analyzed (E). Black arrows indicate heavily pigmented melanocytes. Note that pigmentation was increased after knockdown of Tbx2. Experiments were done in triplicates and error bars were represented as mean ± SD. * indicates P < 0.05, ** indicates P < 0.01, and *** indicates P < 0.001. Scale bar is 50 μm. Supplementary material 2 (JPEG 1272 kb)
11010_2016_2680_MOESM3_ESM.doc (27 kb)
Supplementary material 4 (DOC 27 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Yu Chen
    • 1
  • Li Pan
    • 1
  • Zhongyuan Su
    • 1
  • Jing Wang
    • 1
  • Huirong Li
    • 1
  • Xiaoyin Ma
    • 1
  • Yin Liu
    • 1
  • Fan Lu
    • 2
  • Jia Qu
    • 2
  • Ling Hou
    • 1
    • 2
    Email author
  1. 1.Laboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye HospitalWenzhou Medical UniversityWenzhouChina
  2. 2.State Key Laboratory Cultivation Base and Key Laboratory of Vision Science of Ministry of Health and Zhejiang Provincial Key Laboratory of OphthalmologyWenzhou Medical UniversityWenzhouChina

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