OSTEOCALCIN GENE PROMOTER-BINDING FACTORS ARE TISSUE-SPECIFIC NUCLEAR MATRIX COMPONENTS
OSTEOCALCIN GENE PROMOTER-BINDING FACTORS ARE TISSUE-SPECIFIC NUCLEAR MATRIX COMPONENTS
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DOI：
10.1073/pnas.90.8.3162
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发表时间：
1993-04-15
影响因子：
11.1
通讯作者：
STEIN, GS
中科院分区：
文献类型：
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作者：
BIDWELL, JP;VANWIJNEN, AJ;STEIN, GS
在成骨细胞分化过程中，核基质似乎在发育基因表达中起着重要作用。为了更好地理解这一作用，我们研究了具有序列特异性并与骨钙素基因启动子相互作用的核基质dna结合蛋白。涉及两种不同核基质蛋白的多种蛋白质- dna相互作用发生在5'调控序列（nt -640至-430）内。其中一种蛋白质，NMP-1，是一种普遍存在的细胞生长调节蛋白，与转录因子ATF相关，存在于核基质和非基质核室中。另一种蛋白NMP-2是一种细胞类型特异性的38 kda启动子因子，它识别与CCAAT/增强子结合蛋白C/EBP的一致位点相似的结合位点，并且只定位于核基质上。NMP-1和NMP-2分别与两个核基质蛋白结合元件相互作用。这些元素存在于骨钙素基因启动子的关键调控位点附近，例如主要的类固醇激素（维生素D）响应序列。骨钙素基因启动子在这一区域的结合表明与核基质的短暂结合不同于基质附着区域的稳定相互作用。我们的结果与核基质参与集中和/或定位转录因子一致，这些转录因子介导骨钙素基因转录的基础和类固醇激素反应。
The nuclear matrix appears to play an important role in developmental gene expression during osteoblast differentiation. To better understand this role, we examined nuclear matrix DNA-binding proteins that are sequence-specific and interact with the osteocalcin gene promoter. Multiple protein-DNA interactions involving two distinct nuclear matrix proteins occur within the 5' regulatory sequences (nt -640 to -430). One of these proteins, NMP-1, is a ubiquitous, cell growth-regulated protein that is related to the transcription factor ATF and resides in both the nuclear matrix and the nonmatrix nuclear compartment. The other protein, NMP-2, is a cell type-specific, 38-kDa promoter factor that recognizes binding sites resembling the consensus site for the CCAAT/enhancer-binding protein C/EBP and is localized exclusively on the nuclear matrix. NMP-1 and NMP-2 each interact with two nuclear matrix protein-binding elements. These elements are present near key regulatory sites of the osteocalcin gene promoter, such as the principal steroid hormone (vitamin D)-responsive sequences. Binding in this region of the osteocalcin gene promoter suggests transient associations with the nuclear matrix that are distinct from the stable interactions of matrix attachment regions. Our results are consistent with involvement of the nuclear matrix in concentrating and/or localizing transcription factors that mediate the basal and steroid hormone responsiveness of osteocalcin gene transcription.