Transcriptional regulation of dentin matrix protein 1 by JunB and p300 during osteoblast differentiation
Transcriptional regulation of dentin matrix protein 1 by JunB and p300 during osteoblast differentiation
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DOI：
10.1074/jbc.m403511200
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发表时间：
2004-10-22
影响因子：
4.8
通讯作者：
George, A
中科院分区：
文献类型：
--
作者：
Narayanan, K;Srinivas, R;George, A
牙本质基质蛋白1（Dentin matrix protein 1，DMP 1）是一种酸性非胶原蛋白，主要分布于骨和牙本质的矿化基质中。表达分析表明，DMP 1在成骨细胞和成牙本质细胞中受到差异调节。之前我们报道了c-Fos和c-Jun（AP-1）转录因子对DMP 1的转录调控。早期的研究结果表明c-Fos和c-Jun在成骨细胞的早期分化中起重要作用，而对终末分化的成骨细胞没有显著影响。在本文中，我们展示了一个调节机制，JunB转录控制成骨细胞分化过程中的DMP 1的表达。JunB与p300的协同相互作用已被证明在矿化过程中显著调节DMP 1启动子活性。免疫沉淀和染色质免疫沉淀分析证明了JunB和p300在体内的相互作用。此外，JunB在Ser-79的磷酸化被发现是其与p300相互作用所必需的。p300的内在组蛋白乙酰转移酶活性在调节DMP 1基因表达中也起关键作用。
Dentin matrix protein 1 (DMP1) is an acidic noncollagenous protein localized specifically in the mineralized matrix of bone and dentin. Expression analyses demonstrate that DMP1 is differentially regulated in osteoblasts and odontoblasts. Earlier we have reported on the transcriptional regulation of DMP1 by c-Fos and c-Jun (AP-1) transcription factors. Results from earlier study indicate that c-Fos and c-Jun play an important role in early osteoblast differentiation, whereas they do not have a significant effect on the terminally differentiated osteoblasts. In this paper, we demonstrate a regulatory mechanism by which JunB transcriptionally controls the expression of DMP1 during osteoblast differentiation. The cooperative interaction of JunB with p300 has been shown to dramatically modulate the DMP1 promoter activity during mineralization. Immunoprecipitation and chromatin immunoprecipitation analysis demonstrate the interaction of JunB and p300 in vivo. Further, phosphorylation of JunB at Ser-79 was found to be essential for its interaction with p300. Intrinsic histone acetyltransferase activity of p300 also plays a critical role in regulating DMP1 gene expression.