Stein G S, Lian J B, Dworetzky S I, Owen T A, Bortell R, Bidwell J P, van Wijnen A J
Department of Cell Biology, University of Massachusetts Medical Center, Worcester 01655.
J Cell Biochem. 1991 Dec;47(4):300-5. doi: 10.1002/jcb.240470403.
Several lines of evidence are presented which support involvement of the nuclear matrix in regulating the transcription of two genes, histone and osteocalcin, that are reciprocally expressed during development of the osteoblast phenotype. In the 5' regulatory region of an H4 histone gene, which is expressed in proliferating osteoblasts early during the developmental/differentiation sequence, a dual role is proposed for the nuclear matrix binding domain designated NMP-1 (-589 to -730 upstream from the transcription start site). In addition to functioning as a nuclear matrix attachment site, the sequences contribute to the upregulation of histone gene transcription, potentially facilitated by concentration and localization of an 84kD ATF DNA binding protein. A homologous nuclear matrix binding domain was identified in the promoter of the osteocalcin gene, which is expressed in mature osteoblasts in an extracellular matrix undergoing mineralization. The NMP binding domain in the osteocalcin gene promoter resides contiguous to the vitamin D responsive element. Together with gene and transcription factor localization, a model is proposed whereby nuclear matrix-associated structural constraints on conformation of the osteocalcin gene promoter facilitates vitamin D responsiveness mediated by cooperativity at multiple regulatory elements.
有几条证据表明，核基质参与调控两个基因（组蛋白和骨钙素）的转录，这两个基因在成骨细胞表型发育过程中呈相互表达。在发育/分化序列早期增殖的成骨细胞中表达的H4组蛋白基因的5'调控区域，对于指定为NMP-1（转录起始位点上游-589至-730）的核基质结合域提出了双重作用。除了作为核基质附着位点发挥作用外，这些序列还有助于组蛋白基因转录的上调，这可能由一种84kD的ATF DNA结合蛋白的浓度和定位所促进。在骨钙素基因的启动子中鉴定出一个同源核基质结合域，该基因在经历矿化的细胞外基质中的成熟成骨细胞中表达。骨钙素基因启动子中的NMP结合域与维生素D反应元件相邻。结合基因和转录因子的定位，提出了一个模型，即核基质相关的对骨钙素基因启动子构象的结构限制促进了由多个调控元件的协同作用介导的维生素D反应性。
