LEF-1 Regulates Tyrosinase Gene Transcription In Vitro

Xueping Wang; Yalan Liu; Hongsheng Chen; Lingyun Mei; Chufeng He; Lu Jiang; Zhijie Niu; Jie Sun; Hunjin Luo; Jiada Li; Yong Feng

doi:10.1371/journal.pone.0143142

LEF-1 Regulates Tyrosinase Gene Transcription In Vitro

PLoS One. 2015 Nov 18;10(11):e0143142. doi: 10.1371/journal.pone.0143142. eCollection 2015.

Authors

Xueping Wang¹, Yalan Liu², Hongsheng Chen^{1

2}, Lingyun Mei^{1

2}, Chufeng He^{1

2}, Lu Jiang^{1

2}, Zhijie Niu¹, Jie Sun^{1

3}, Hunjin Luo⁴, Jiada Li⁴, Yong Feng^{1

2

4}

Affiliations

¹ Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
² Province Key Laboratory of Otolaryngology Critical Disease, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
³ Department of Otolaryngology, 1st Affiliated Hospital, Xinjiang Medical University, Urumqi, People's Republic of China.
⁴ State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, People's Republic of China.

Abstract

TYR, DCT and MITF are three important genes involved in maintaining the mature phenotype and producing melanin; they therefore participate in neural crest cell development into melanocytes. Previous studies have revealed that the Wnt signaling factor lymphoid enhancer-binding factor (LEF-1) can enhance DCT and MITF gene expression. However, whether LEF-1 also affects TYR gene expression remains unclear. In the present study, we found that LEF-1 regulated TYR transcription in vitro. LEF-1 overexpression increased TYR gene promoter activity, whereas LEF-1 knockdown by RNA interference significantly decreased TYR expression. Moreover, the core GTTTGAT sequence (-56 to -50) within the TYR promoter is essential for the effect of LEF-1 on TYR expression, and chromatin immunoprecipitation (ChIP) assay indicated that endogenous LEF-1 interacts with the TYR promoter. In addition, we observed a synergistic transactivation of the TYR promoter by LEF-1 and MITF. These data suggest that Wnt signaling plays an important role in regulating melanocyte development and differentiation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Binding Sites
Cell Differentiation
Chromatin / chemistry
Chromatin / metabolism
Chromatin Immunoprecipitation
Gene Expression Regulation
HEK293 Cells
HeLa Cells
Humans
Intramolecular Oxidoreductases / genetics
Intramolecular Oxidoreductases / metabolism
Lymphoid Enhancer-Binding Factor 1 / antagonists & inhibitors
Lymphoid Enhancer-Binding Factor 1 / genetics*
Lymphoid Enhancer-Binding Factor 1 / metabolism
Melanocytes / cytology
Melanocytes / metabolism*
Mice
Microphthalmia-Associated Transcription Factor / genetics*
Microphthalmia-Associated Transcription Factor / metabolism
Molecular Sequence Data
Monophenol Monooxygenase / genetics*
Monophenol Monooxygenase / metabolism
NIH 3T3 Cells
Nucleotide Motifs
Promoter Regions, Genetic
Protein Binding
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Transcription, Genetic
Wnt Signaling Pathway*

Substances

Chromatin
LEF1 protein, human
Lymphoid Enhancer-Binding Factor 1
MITF protein, human
Microphthalmia-Associated Transcription Factor
RNA, Small Interfering
Monophenol Monooxygenase
Intramolecular Oxidoreductases
dopachrome isomerase

Grants and funding

This study was supported by National Basic Research and Development Program of China (973 Program) (No. 2014CB541702, to Yong Feng), the National Natural Science Foundation of China (Nos. 81170923, 81470705 to Yong Feng; No. 81300833 to Lu Jiang), The public welfare industry research special fund projects of ministry of health of China (No. 201302001, to Yong Feng). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.