Distal cis-regulatory elements are required for tissue-specific expression of enamelin (Enam)
Distal cis-regulatory elements are required for tissue-specific expression of enamelin (Enam)
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DOI：
10.1111/j.1600-0722.2007.00519.x
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发表时间：
2008-04-01
影响因子：
1.9
通讯作者：
Hu, Jan C-C.
中科院分区：
文献类型：
--
作者：
Hu, Yuanyuan;Papagerakis, Petros;Hu, Jan C-C.
釉质的形成是由编码釉质基质蛋白的基因的顺序表达来协调的;然而，在釉质形成过程中维持基因转录的时空顺序的机制却知之甚少。本研究的目的是表征正常表达的釉蛋白（Enam）所必需的顺式调控序列。几个釉蛋白转录调控区，物种之间表现出较高的序列同源性，被确定。将含有釉蛋白翻译起始位点上游的5.2或3.9 kb区域的DNA构建体与LacZ报告基因连接，并用于产生转基因小鼠。只有5.2-Enam-LacZ构建体足以概括釉蛋白牙齿特异性表达的内源性模式。3.9-Enam-LacZ转基因株在牙细胞中不表达，但在成骨细胞中检测到异位β-半乳糖苷酶活性。潜在的转录因子结合位点被确定，可能是重要的控制釉蛋白基础启动子活性，并赋予釉蛋白组织特异性表达。我们的研究为釉蛋白表达的调控机制提供了新的见解。
Enamel formation is orchestrated by the sequential expression of genes encoding enamel matrix proteins; however, the mechanisms sustaining the spatio-temporal order of gene transcription during amelogenesis are poorly understood. The aim of this study was to characterize the cis-regulatory sequences necessary for normal expression of enamelin (Enam). Several enamelin transcription regulatory regions, showing high sequence homology among species, were identified. DNA constructs containing 5.2 or 3.9 kb regions upstream of the enamelin translation initiation site were linked to a LacZ reporter and used to generate transgenic mice. Only the 5.2-Enam-LacZ construct was sufficient to recapitulate the endogenous pattern of enamelin tooth-specific expression. The 3.9-Enam-LacZ transgenic lines showed no expression in dental cells, but ectopic beta-galactosidase activity was detected in osteoblasts. Potential transcription factor-binding sites were identified that may be important in controlling enamelin basal promoter activity and in conferring enamelin tissue-specific expression. Our study provides new insights into regulatory mechanisms governing enamelin expression.