Identification of the Novel Tooth-Specific Transcription Factor AmeloD
Identification of the Novel Tooth-Specific Transcription Factor AmeloD
复制标题
新型牙齿特异性转录因子 AmeloD 的鉴定
DOI：
10.1177/0022034518808254
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发表时间：
2019-02-01
影响因子：
7.6
通讯作者：
Yamada, Y.
中科院分区：
文献类型：
--
作者：
He, B.;Chiba, Y.;Yamada, Y.
碱性螺旋环螺旋（bHLH）转录因子在各种器官的发育中起着重要的作用，然而，牙齿特异性bHLH因子尚未报道。在这项研究中，我们确定了一个新的牙齿特异性bHLH转录因子，我们命名为AmeloD，通过筛选牙胚互补DNA（cDNA）文库，使用酵母双杂交系统。AmeloD定位于小鼠染色体1 q32。系统发育分析表明AmeloD属于无毛鳞片复合体样（ASCL）基因家族，与ASCL 5同源。AmeloD只在内釉上皮细胞中表达，但其表达在内釉上皮细胞分化为成釉细胞后被抑制。此外，AmeloD的表达与牙上皮中上皮细胞特异性细胞-细胞粘附分子E-cadherin的表达模式相反。在牙上皮细胞系CLDE细胞中AmeloD的过表达导致E-钙粘蛋白的抑制。我们发现AmeloD与E-cadherin基因近端启动子区的E-box顺式调控元件结合。这些结果表明AmeloD在IEE细胞中作为E-钙粘蛋白转录的抑制剂发挥作用。我们的研究表明AmeloD是一种新的牙齿特异性bHLH转录因子，可能通过抑制IEE细胞中的E-cadherin来调节牙齿发育。
Basic-helix-loop-helix (bHLH) transcription factors play an important role in various organs' development; however, a tooth-specific bHLH factor has not been reported. In this study, we identified a novel tooth-specific bHLH transcription factor, which we named AmeloD, by screening a tooth germ complementary DNA (cDNA) library using a yeast 2-hybrid system. AmeloD was mapped onto the mouse chromosome 1q32. Phylogenetic analysis showed that AmeloD belongs to the achaete-scute complex-like (ASCL) gene family and is a homologue of ASCL5. AmeloD was uniquely expressed in the inner enamel epithelium (IEE), but its expression was suppressed after IEE cell differentiation into ameloblasts. Furthermore, AmeloD expression showed an inverse expression pattern with the epithelial cell-specific cell-cell adhesion molecule E-cadherin in the dental epithelium. Overexpression of AmeloD in dental epithelial cell line CLDE cells resulted in E-cadherin suppression. We found that AmeloD bound to E-box cis-regulatory elements in the proximal promoter region of the E-cadherin gene. These results reveal that AmeloD functions as a suppressor of E-cadherin transcription in IEE cells. Our study demonstrated that AmeloD is a novel tooth-specific bHLH transcription factor that may regulate tooth development through the suppression of E-cadherin in IEE cells.