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Molecular analysis of the nerve growth factor inducible ornithine decarboxylase gene in PC12 cells
Author(s) -
Muller S. R.,
Huff S. Y.,
Goode B. L.,
Marschall L.,
Chang J.,
Feinstein Stuart C.
Publication year - 1993
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490340307
Subject(s) - ornithine decarboxylase , biology , nerve growth factor , transcriptional regulation , ornithine decarboxylase antizyme , gene , promoter , transcription factor , microbiology and biotechnology , gene expression , primer extension , regulation of gene expression , genetics , messenger rna , biochemistry , enzyme , receptor
Abstract In an effort to understand molecular mechanisms by which nerve growth factor (NGF) regulates gene expression, we have isolated a full‐length rat cDNA clone encoding ornithine decarboxylase (ODC) and utilized this probe to identify and examine the transcriptionally active, NGF inducible ODC gene in rat PC12 cells. This same gene is also responsive to epidermal growth factor, basic fibroblast growth factor, and dibutyryl cAMP. Primer extension analysis demonstrates that both basal and NGF induced transcription of the ODC gene utilize the same major transcriptional start site, demonstrating that NGF acts to increase transcriptional activity at the basal start site as opposed to unmasking an alternative, stronger start site. Functional promoter analysis reveals the presence of a constitutive core promoter residing between positions −201 and +390, relative to the start site of transcription. Additional analyses reveal that sequences in the region −7800 to +2257 are insufficient to mediate NGF induced transcriptional activation, demonstrating that at least some of the regulatory sequences necessary for NGF mediated transcriptional induction of the ODC gene must reside at relatively enormous distances from the transcriptional start site. Such a long distance transcriptional regulatory mechanism is unique when compared with other NGF responsive genes that have been similarly analyzed. © 1993 Wiley‐Liss, Inc.