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学科主题基础医学
Transcriptional Factor DLX3 Promotes the Gene Expression of Enamel Matrix Proteins during Amelogenesis
Zhang, Zhichun1; Tian, Hua1; Lv, Ping1; Wang, Weiping2; Jia, Zhuqing2; Wang, Sainan1; Zhou, Chunyan2; Gao, Xuejun1
刊名PLOS ONE
2015-03-27
DOI10.1371/journal.pone.0121288
10期:3
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]DIFFERENTIATION ; IMPERFECTA ; MUTATION ; DELETION ; CELLS ; HOMEOPROTEINS ; PHENOTYPE ; LINEAGE ; MURINE
英文摘要

Mutation of distal-less homeobox 3 (DLX3) is responsible for human tricho-dento-osseous syndrome (TDO) with amelogenesis imperfecta, indicating a crucial role of DLX3 in amelogenesis. However, the expression pattern of DLX3 and its specific function in amelogenesis remain largely unknown. The aim of this study was to investigate the effects of DLX3 on enamel matrix protein (EMP) genes. By immunohistochemistry assays of mouse tooth germs, stronger immunostaining of DLX3 protein was identified in ameloblasts in the secretory stage than in the pre-secretory and maturation stages, and the same pattern was found for Dlx3 mRNA using Realtime PCR. In a mouse ameloblast cell lineage, forced expression of DLX3 up-regulated the expression of the EMP genes Amelx, Enam, Klk4, and Odam, whereas knockdown of DLX3 down-regulated these four EMP genes. Further, bioinformatics, chromatin immunoprecipitation, and luciferase assays revealed that DLX3 transactivated Enam, Amelx, and Odam through direct binding to their enhancer regions. Particularly, over-expression of mutant-DLX3 (c.571_574delGGGG, responsible for TDO) inhibited the activation function of DLX3 on expression levels and promoter activities of the Enam, Amelx, and Odam genes. Together, our data show that DLX3 promotes the expression of the EMP genes Amelx, Enam, Klk4, and Odam in amelogenesis, while mutant-DLX3 disrupts this regulatory function, thus providing insights into the molecular mechanisms underlying the enamel defects of TDO disease.

语种英语
WOS记录号WOS:000352133600081
项目编号NSFC 81300839 ; 20130001120109
资助机构National Natural Science Foundation of China ; Specialized Research Fund for the Doctoral Program of Higher Education
引用统计
被引频次:7[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64777
专题北京大学口腔医学院_牙体牙髓科
北京大学基础医学院
北京大学第一临床医学院_人事处
作者单位1.Peking Univ, Sch & Hosp Stomatol, Dept Cariol & Endodontol, Beijing 100871, Peoples R China
2.Peking Univ, Dept Biochem & Mol Biol, Sch Basic Med Sci, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
Zhang, Zhichun,Tian, Hua,Lv, Ping,et al. Transcriptional Factor DLX3 Promotes the Gene Expression of Enamel Matrix Proteins during Amelogenesis[J]. PLOS ONE,2015,10(3).
APA Zhang, Zhichun.,Tian, Hua.,Lv, Ping.,Wang, Weiping.,Jia, Zhuqing.,...&Gao, Xuejun.(2015).Transcriptional Factor DLX3 Promotes the Gene Expression of Enamel Matrix Proteins during Amelogenesis.PLOS ONE,10(3).
MLA Zhang, Zhichun,et al."Transcriptional Factor DLX3 Promotes the Gene Expression of Enamel Matrix Proteins during Amelogenesis".PLOS ONE 10.3(2015).
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