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学科主题: 基础医学
题名:
Transcriptional Factor DLX3 Promotes the Gene Expression of Enamel Matrix Proteins during Amelogenesis
作者: Zhang, Zhichun1; Tian, Hua1; Lv, Ping1; Wang, Weiping2; Jia, Zhuqing2; Wang, Sainan1; Zhou, Chunyan2; Gao, Xuejun1
刊名: PLOS ONE
发表日期: 2015-03-27
DOI: 10.1371/journal.pone.0121288
卷: 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
所属项目编号: NSFC 81300839 ; 20130001120109
项目资助者: National Natural Science Foundation of China ; Specialized Research Fund for the Doctoral Program of Higher Education
WOS记录号: WOS:000352133600081
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64777
Appears in Collections:基础医学院_期刊论文

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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

Recommended Citation:
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).
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