The CCAAT Enhancer-binding Protein (C/EBP) (cid:1) and Nrf1 Interact to Regulate Dentin Sialophosphoprotein ( DSPP ) Gene Expression during Odontoblast Differentiation*
The CCAAT Enhancer-binding Protein (C/EBP) (cid:1) and Nrf1 Interact to Regulate Dentin Sialophosphoprotein ( DSPP ) Gene Expression during Odontoblast Differentiation*
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发表时间：
2004
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通讯作者：
K. Narayanan;A. Ramachandran;M. Peterson;J. Hao;A. Kolstø;A. Friedman;A. George
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作者：
K. Narayanan;A. Ramachandran;M. Peterson;J. Hao;A. Kolstø;A. Friedman;A. George
成牙本质细胞是牙本质形成的主要细胞，其终末分化是通过合成I型胶原和非胶原蛋白完成的。DSP和DPP是终末分化成牙本质细胞的特异性标志物，由单基因DSPP（dentin sialophosphoprotein）编码。在试图了解DSPP基因的组织特异性表达所需的分子机制，我们已经确定了两个bZIP转录因子，Nrf 1和CCAAT增强子结合蛋白（C/ EBP）之间的新的相互作用（同上：1）。免疫沉淀和染色质免疫沉淀试验证实了这种相互作用。在未分化的成牙本质细胞中，Nrf 1和C/EBP（cid：1）通过相互作用单独或协同抑制DSPP启动子活性。这种相互作用是由两种蛋白质中的bZIP结构域促进的。确定了Nrf 1和C/EBP（cid：1）中的抑制结构域，并且该结构域的缺失消除了转录抑制。
Terminal differentiation of odontoblasts, the princi-pal cells in dentin formation, proceeds by synthesis of type I collagen and noncollagenous proteins. DSP and DPP are specific markers for terminally differentiated odontoblasts and are encoded by a single gene DSPP (dentin sialophosphoprotein). In an attempt to understand the molecular mechanisms required for tissue-specific expression of the DSPP gene, we have identified a novel interaction between two bZIP transcription factors, Nrf1 and the CCAAT enhancer-binding protein (C/ EBP) (cid:1) . This interaction was confirmed by both immunoprecipitation and chromatin immunoprecipitation assays. In undifferentiated odontoblasts, Nrf1 and C/EBP (cid:1) repress DSPP promoter activity individually and synergistically by cooperatively interacting with each other. This mutual interaction is facilitated by the bZIP domains in both the proteins. The repression domain in both Nrf1 and C/EBP (cid:1) was determined, and deletion of this domain abolished transcriptional repression.