Abstract
We have studied nerve growth factor (NGF) regulation of the expression of the tyrosine hydroxylase (TH) gene in PC12 cells. The TH gene encodes the initial and rate-limiting enzyme of the catecholamine biosynthetic pathway. We show that the TH gene is transiently transcriptionally induced by a mechanism reliant on new protein synthesis during 1-2 hr of NGF stimulation, a time following the induction of the c-fos gene at 15 min post-NGF treatment. A potential regulatory sequence located within the TH gene promoter, the TH-FSE, shares homology to a known regulatory element, the fat-specific element (FSE), which is found upstream from genes activated during adipocyte differentiation and binds the Fos-Jun transcription factor complex. We show that the TH-FSE DNA sequence elevates the basal level of transcription from the rat TH promoter and is required for NGF inducibility. This DNA element binds authentic Fos-Jun products produced abundance during NGF stimulation and by in vitro translation. We demonstrate further that the TH-FSE can bind proteins present in PC12 nuclear extracts in a sequence-specific manner. The DNA/nucleoprotein complex that forms increases in abundance during NGF stimulation and reaches a maximum level at 4 hr of treatment. Antibody inhibition studies utilizing an anti-Fos antibody indicate that Fos and/or Fos-related antigen(s) associate with the TH-FSE and suggest that the Fos protein family contributes to the regulation of TH in vivo. These results support a model in which NGF-induced immediate early genes, including c-Fos, contribute to the regulation of delayed early genes such as TH and thereby control neuronal differentiation.
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Dates
Type | When |
---|---|
Created | 18 years, 2 months ago (June 5, 2007, 5:15 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 13, 2021, 11:08 p.m.) |
Indexed | 1 month, 1 week ago (July 20, 2025, 6:55 p.m.) |
Issued | 35 years, 4 months ago (April 1, 1990) |
Published | 35 years, 4 months ago (April 1, 1990) |
Published Online | 35 years, 4 months ago (April 1, 1990) |
Published Print | 35 years, 4 months ago (April 1, 1990) |
@article{Gizang_Ginsberg_1990, title={Nerve growth factor regulates tyrosine hydroxylase gene transcription through a nucleoprotein complex that contains c-Fos.}, volume={4}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.4.4.477}, DOI={10.1101/gad.4.4.477}, number={4}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Gizang-Ginsberg, E and Ziff, E B}, year={1990}, month=apr, pages={477–491} }