Johnson-Pais T L, Leach R J
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284.
Somat Cell Mol Genet. 1992 Sep;18(5):423-30. doi: 10.1007/BF01233082.
We have constructed a series of interspecific somatic cell hybrids between the human osteoblast-like osteosarcoma, TE85, and a mouse fibrosarcoma, La-t-. In these whole-cell hybrids, we observed a 10-fold reduction of human liver/bone/kidney (L/B/K) alkaline phosphatase steady-state mRNA and alkaline phosphatase protein activity. The phenomenon of loss of tissue-specific gene expression has been termed extinction. Subclones of these hybrids were isolated, which reexpressed the alkaline phosphatase gene product. These late-passage hybrids had a reduced number of mouse fibroblast chromosomes when compared to earlier passages. This suggests that a trans-acting negative regulatory element, encoded in the fibroblast genome, regulates expression of L/B/K alkaline phosphatase. This is the first evidence that extinction plays a role in the regulation of osteoblast gene expression.
我们构建了一系列人成骨细胞样骨肉瘤细胞系TE85与小鼠纤维肉瘤细胞系La-t-之间的种间体细胞杂种。在这些全细胞杂种中，我们观察到人类肝/骨/肾（L/B/K）碱性磷酸酶稳态mRNA和碱性磷酸酶蛋白活性降低了10倍。组织特异性基因表达丧失的现象被称为基因消减。分离出这些杂种的亚克隆，它们重新表达了碱性磷酸酶基因产物。与早期传代的杂种相比，这些晚期传代的杂种含有较少数量的小鼠成纤维细胞染色体。这表明成纤维细胞基因组中编码的一种反式作用负调控元件调节L/B/K碱性磷酸酶的表达。这是基因消减在成骨细胞基因表达调控中起作用的首个证据。
