Xanthopoulos K G, Mirkovitch J, Decker T, Kuo C F, Darnell J E
Molecular Cell Biology Laboratory, Rockefeller University, New York, NY 10021.
Proc Natl Acad Sci U S A. 1989 Jun;86(11):4117-21. doi: 10.1073/pnas.86.11.4117.
The mRNA encoding the mouse homolog of C/EBP, a rat DNA-binding protein that participates in activating a number of genes in hepatocytes, is present in liver cells at a far higher concentration than in most other cells, including spleen, kidney, muscle, and the majority of the brain. However, fat cells and intestinal cells contain 25-50% as much mRNA as liver cells. "Run-on" experiments show that the basis for the restricted cellular distribution of the mouse C/EBP mRNA is transcriptional regulation of the gene. We also show that disruption of cell-cell contacts incident to liver cell dispersion results in a prompt and extensive reduction in mouse C/EBP transcription as we had earlier shown to be the case for a group of 10 genes transcribed in a hepatocyte-specific fashion. In contrast, breaking cell contacts and plating the hepatocytes in culture leads to a prolonged increase in transcription of the Jun-B gene that encodes a widely distributed transcription factor. These results illustrate that the regulation of expression of a mammalian regulatory protein with limited tissue distribution is controlled at the level of transcription and depends on cell contacts.
编码C/EBP小鼠同源物的信使核糖核酸(mRNA),C/EBP是一种大鼠DNA结合蛋白,参与激活肝细胞中的许多基因,在肝细胞中的浓度远高于大多数其他细胞,包括脾脏、肾脏、肌肉和大部分脑组织。然而,脂肪细胞和肠细胞所含的mRNA量是肝细胞的25%-50%。“连续转录”实验表明,小鼠C/EBP mRNA细胞分布受限的基础是该基因的转录调控。我们还表明,与肝细胞分散相关的细胞间接触的破坏会导致小鼠C/EBP转录迅速而广泛地减少,正如我们之前所表明的,一组以肝细胞特异性方式转录的10个基因也是如此。相反,破坏细胞接触并将肝细胞接种到培养基中会导致编码广泛分布的转录因子的Jun-B基因转录长期增加。这些结果表明,具有有限组织分布的哺乳动物调节蛋白的表达调控在转录水平上受到控制,并依赖于细胞接触。