A C/EBP-binding site in the transferrin promoter is essential for expression in the liver but not the brain of transgenic mice
| Autor: | G G Cadd, M. Theisen, Ralph L. Brinster, Richard R. Behringer, G. S. Mcknight |
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| Rok vydání: | 1993 |
| Předmět: |
Male
Genetically modified mouse Transcription Genetic Transgene Molecular Sequence Data Mice Transgenic Biology Mice Transcription (biology) Animals Humans Tissue Distribution Binding site Promoter Regions Genetic Molecular Biology Gene Sequence Deletion chemistry.chemical_classification Binding Sites Base Sequence Ccaat-enhancer-binding proteins Transferrin Brain Nuclear Proteins Promoter DNA Cell Biology Molecular biology DNA-Binding Proteins Mice Inbred C57BL Liver chemistry CCAAT-Enhancer-Binding Proteins Female Research Article |
| Zdroj: | Molecular and Cellular Biology. 13:7666-7676 |
| ISSN: | 1098-5549 0270-7306 |
| DOI: | 10.1128/mcb.13.12.7666 |
| Popis: | The gene for the iron-binding protein transferrin is transcribed at a high level in liver hepatocytes but is also active in several other cell types, including oligodendrocytes in the brain. Enhancer elements between bp -560 and -44 of the transferrin gene promoter specifically activated transcription from a heterologous promoter in transgenic mouse liver and brain. Within this region, a potent cis-acting element between bp -98 and -83 was found to be essential for gene activity in both cultured hepatocytes and transgenic mouse liver. The -98 to -83 element contains a CCAAT sequence and is specifically bound by a nuclear factor from mouse liver that is homologous to rat liver C/EBP (CAAT enhancer-binding protein). Point mutations within this binding site inhibit factor binding and abolish transcription in transfected hepatoma cells. When placed in the context of the 3,000-bp transferrin promoter, the C/EBP binding site mutation causes a complete loss of transcription in transgenic mouse liver; however, transgene expression in the brain of the same animals was unaffected. These results suggest a modular structure for the transferrin promoter and demonstrate that deletions or specific point mutations can be used to generate transgene promoters with an activity more restricted than that of their endogenous counterparts. |
| Databáze: | OpenAIRE |
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