Hepatocyte nuclear factor-4 activates medium chain acyl-CoA dehydrogenase gene transcription by interacting with a complex regulatory element
| Autor: | M E, Carter, T, Gulick, B D, Raisher, T, Caira, J A, Ladias, D D, Moore, D P, Kelly |
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| Rok vydání: | 1993 |
| Předmět: |
Binding Sites
Receptors Thyroid Hormone Base Sequence Transcription Genetic Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Molecular Sequence Data Tretinoin 3T3 Cells Regulatory Sequences Nucleic Acid Phosphoproteins Transfection Acyl-CoA Dehydrogenase Gene Expression Regulation Enzymologic Recombinant Proteins Rats DNA-Binding Proteins Mice Acyl-CoA Dehydrogenases Hepatocyte Nuclear Factor 4 Animals Promoter Regions Genetic Transcription Factors |
| Zdroj: | The Journal of biological chemistry. 268(19) |
| ISSN: | 0021-9258 0264-2026 |
| Popis: | We have recently identified a complex transcriptional regulatory element in the medium chain acyl-CoA dehydrogenase (MCAD) gene promoter region that confers response to retinoids through interaction with receptors for all-trans-retinoic acid (RARs) and 9-cis-retinoic acid (RXRs) (Raisher, B. D., Gulick, T., Zhang, Z., Strauss, A. W., Moore, D. D., and Kelly, D. P. (1992) J. Biol. Chem. 267, 20264-20269). We examined the interaction of this element (RAREMCAD) with hepatocyte nuclear factor-4 (HNF-4), an orphan receptor with a tissue expression pattern similar to that of MCAD. Electrophoretic mobility shift assays and cotransfection experiments showed that HNF-4 binds with high affinity to RAREMCAD to activate transcription by an RXR-independent mechanism. Mutational analysis revealed that the MCAD HNF-4 response element consists of an imperfect direct repeat homologous to the consensus sequence for binding to the thyroid receptor/RAR/RXR subgroup of receptors and that distinct sequence requirements dictate HNF-4 binding and transactivation. Mobility shift assays with anti-HNF-4 antiserum demonstrated that the MCAD HNF-4 response element binds endogenous rat liver HNF-4 supporting its role in the regulation of MCAD gene expression in vivo. Thus, HNF-4 activates MCAD gene transcription via a complex regulatory element, the architecture of which carries important implications for the structure of HNF-4 response elements in general. |
| Databáze: | OpenAIRE |
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