Ability of Egr1 to activate tyrosine hydroxylase transcription in PC12 cells: Cross-talk with AP-1 factors

N. A. Papanikolaou, E. L. Sabban

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


We have recently identified an Egr1 motif that overlaps with the Sp1 element in the tyrosine hydroxylase (TH) promoter. Here we examine whether this motif has a functional role in the regulation of TH transcription in PC12 cells. In nuclear extracts from control PC12 cells, an oligonucleotide containing the TH Sp1/Egr1 motif binds Sp1-containing complexes. Treatment of PC12 cells with phorbol ester (2 μM 12-O-tetradecanoylphorbol-13-acetate (TPA)) gives rise to a new Egr1-containing complex. TPA treatment reduces the steady-state levels of the Sp1 protein and leads to the appearance of immunoreactive Egr1 protein within 30-60 min. Expression of the Egr1 protein in PC12 cells stimulates the chloramphenicol acetyltransferase reporter gene placed under the control of the first 272 nucleotides of the rat TH promoter. Site-directed mutagenesis of either the Sp1/Egr1 motif or of an upstream AP-1 motif or both abolishes the Egr1-mediated induction of chloramphenicol acetyltransferase activity. An oligonucleotide encompassing the AP-1/E-box sequence of the rat TH promoter competes in electrophoretic mobility shift assays for binding of nuclear extracts from control and TPA-treated cells to an oligonucleotide containing the Sp1/Egr1 element, indicating that these two enhancers may interact. The results show that Egr1 can activate TH transcription and reveals cross-talk between Sp1/Egr1 and AP-1 factors.

Original languageEnglish (US)
Pages (from-to)26683-26689
Number of pages7
JournalJournal of Biological Chemistry
Issue number35
StatePublished - Sep 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry


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