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http://dx.doi.org/10.5352/JLS.2007.17.2.167

Genomic Organization and Promoter Characterization of the Murine Glial Cell-derived Neurotrophic Factor Inducible Transcription Factor (mGIF) Gene  

Kim, Ok-Soo (Department of Pharmaceutical Engineering, College of Medical Life Science, University)
Kim, Yong-Man (FCB-Pharmicell Co., LTD)
Kim, Nam-Young (Department of Pharmaceutical Engineering, College of Medical Life Science, University)
Lee, Eo-Jin (Department of Pharmaceutical Engineering, College of Medical Life Science, University)
Jang, Min-Kyung (Department of Pharmaceutical Engineering, College of Medical Life Science, University)
Lee, Dong-Geun (Department of Pharmaceutical Engineering, College of Medical Life Science, University)
Lee, Sang-Hyeon (Department of Pharmaceutical Engineering, College of Medical Life Science, University)
Publication Information
Journal of Life Science / v.17, no.2, 2007 , pp. 167-173 More about this Journal
Abstract
To study the transcriptional mechanisms by which expression of the murine glial cell-derived neurotrophic factor inducible transcription factor (mGIF) gene is regulated, a murine genomic clone was iso-lated using a mGIF cDNA as probe. A 13-kb genomic fragment, which comprises 4-kb upstream of the transcription initiation site was sequenced. The promoter region lacks a TATA box and CAAT box, is rich in G+C content, and has multiple putative binding sites for the transcription factor Spl. The mGIF gene also has consensus sequences for AP2 binding sites. The transcriptional activity of five deletion mutants of a 2.1-kb fragment was analyzed by modulating transcription of the heterologous luciferase gene in the promoterless plasmid pGL2-Basic. All mutants showed significant transcriptional activity in the murine neuroblastoma cell line NB41A3. Transient expression assays suggested the presence of a positive regulator between -213 and -129 while a negative regulator was found in the region between -806 and -214. Relatively strong transcriptional activity was observed in neuronal NB41A3, glial C6 cells and hepatic HepG2, but very weak activity in skeletal muscle C2C12 cells. These findings confirm the tissue-specific activity of the mGIF promoter and suggest that this gene shares structural and functional similarities with the dopamine receptor genes that it regulates.
Keywords
Regulation; Sp1; TATA-less; transcription factor;
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1 Minowa, M. T., T. Minowa, F. J. Monsma Jr., D. R. Sibley and M. M. Mouradian. 1992. Characterization of the 5'flanking region of the human $D_{1A}$ dopamine receptor gene. Proc. Natl. Acad. Sci., USA 89, 3045-3049   DOI   ScienceOn
2 Minowa, M. T., T. Minowa and M. M. Mouradian. 1993. Activator region analysis of the human $D_{1A}$ dopamine receptor gene. J. Biol. Chem. 268, 23544-23551
3 Minowa, T., M. T. Minowa and M. M. Mouradian. 1992. Characterization of the 5'-flanking region of the human $D_2$ dopamine receptor gene. Biochem. 31, 8389-8396   DOI   ScienceOn
4 Minowa, T., M. T. Minowa and M. M. Mouradian. 1994. Negative modulator of the rat $D_2$ dopamine receptor gene. J. Biol. Chem. 269, 11656-11662
5 Roesler, W. J., G. R. Vandenbark and R. W. Hanson. 1988. Cyclic AMP and the induction of eukaryotic gene transcription. J. Biol. Chem. 263, 9063-9066
6 Sambrook, J., E. F. Fritsch and T. Maniatis. 1989. Molecular Cloning: A Laboratory Manual, 2nd Ed., Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA
7 Sanger, F., S. Nicklen and A. R. Coulson. 1977. DNA sequencing with chain-terminating inhibitors. Proc. Natl. Acad. Sci. USA 74, 5463-5467   DOI   ScienceOn
8 Sauerwald, A., C. Hoesche, R. Oschwald and M. W. Kilimann, M. W. 1990. The 5'-flanking region of the synapsin I gene. A G+C-rich, TATA- and CAAT-less, phylogenetically conserved sequence with cell type-specific promoter function. J. Biol. Chem. 265, 14932-14937
9 Sehgal, A., N. Patil and M. Chao. 1988. A constitutive promoter directs expression of the nerve growth factor receptor gene. Mol. Cell. Biol. 8, 3160-3167   DOI
10 Yajima, S., C.-H. Lammers, S.-H. Lee, Y. Hara, K. Mizuno and M. M. Mouradian. 1997. Cloning and characterization of murine gial cell-derived neurotrophic factor inducible transcription factor (mGIF). J. Neurosci. 17, 8657-8666   DOI
11 Heinz, A. 2002. Dopaminergic dysfunction in alcoholism and schizophrenia-psychopathological and behavioral correlates. Eur. Psychiatry. 17, 9-16
12 Jentsch, J. D., R. H. Roth and J. R. Taylor. 2000. Role for dopamine in the behavioral functions of the prefrontal corticostriatal system: implications for mental disorders and psychotropic drug action. Prog. Brain Res. 126, 433-453   DOI   ScienceOn
13 Lee, S.-H., W. Wang, S. Yajima, P. A Jose and M. M. Mouradian. 1997. Tissue-specific promoter usage in the $D_{1A}$ dopamine receptor gene in brain and kidney. DNA Cell Biol. 16, 1267-1275   DOI   ScienceOn
14 Kaczynski, J. A., A A Conley, M. Fernandez Zapico, S. M. Delgado, J. S. Zhang and R. A. Urrutia. 2002. Functional analysis of BTEB3 and BTEB4, a novel Sp1-like protein, reveal a subfamily of transcriptional repressors for the BTE site of the P4501A1 gene promoter. Biochem. J. 366, 873-882   DOI
15 Kadonaga, J. T., K. R. Carner, F. R. Masiarz and R. Tjian. 1987. Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain. Cell 51, 1079-1090   DOI   ScienceOn
16 Lee, S.-H., M. T. Minowa and M. M. Mouradian. 1996. Two distinct promoters derive transcription of the human $D_{1A}$ dopamine receptor gene. J. Biol. Chem. 271, 25292-25299   DOI   ScienceOn
17 Lee, S.-H. Y.-M. Kim, S. Yajima, J.-M. Ha, B. J. Ha, O. S. Kim, K. Ohsawa and M. M. Mouradian. 2003. Genomic organization and promoter characterization of the murine dopamine receptor regulating factor (DRRF) gene. Gene 203, 193-199