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The cyclic AMP response element directs tyrosine hydroxylase expression in catecholaminergic central and peripheral nervous system cell lines from transgenic mice.

Publication ,  Journal Article
Lazaroff, M; Patankar, S; Yoon, SO; Chikaraishi, DM
Published in: J Biol Chem
September 15, 1995

Enhancer elements regulating the neuronal gene, tyrosine hydroxylase (TH), were identified in TH-expressing peripheral nervous system PATH and central nervous system CATH cell lines. Mutational analysis in which rat TH 5'-flanking sequences directed chloramphenicol acetyltransferase (CAT) reporter gene expression demonstrated that mutating the cyclic AMP response element (CRE) at -45 base pair reduced expression by 80-90%. A CRE linked to an enhancerless TH promoter fully supported expression. Cotransfection of a dominant-negative CREB protein reduced expression 50-60%, suggesting that the CRE is bound by CREB or a CREB dimerization partner. Although mutating the AP1/dyad (AD) element at -205 base pair only modestly reduced CAT levels, AD minimal enhancer constructs gave 45-80% of wild type expression when positioned at -91 or -95. However, in its native context at -205, the AD could not support expression. In contrast, a CRE, moved from its normal position at -45 to -206, gave full activity. These results indicate that the CRE is critical for TH transcription in central nervous system CATH and peripheral nervous system PATH cells, whereas the AD is less important and its enhancer activity is context-and/or position-dependent. These results represent the first attempts to map regulatory elements directing TH expression in central nervous system cell lines.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

September 15, 1995

Volume

270

Issue

37

Start / End Page

21579 / 21589

Location

United States

Related Subject Headings

  • Tyrosine 3-Monooxygenase
  • Transfection
  • Transcription, Genetic
  • Restriction Mapping
  • Recombinant Proteins
  • Rats
  • Promoter Regions, Genetic
  • Peripheral Nerves
  • Mutagenesis
  • Molecular Sequence Data
 

Citation

APA
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ICMJE
MLA
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Lazaroff, M., Patankar, S., Yoon, S. O., & Chikaraishi, D. M. (1995). The cyclic AMP response element directs tyrosine hydroxylase expression in catecholaminergic central and peripheral nervous system cell lines from transgenic mice. J Biol Chem, 270(37), 21579–21589. https://doi.org/10.1074/jbc.270.37.21579
Lazaroff, M., S. Patankar, S. O. Yoon, and D. M. Chikaraishi. “The cyclic AMP response element directs tyrosine hydroxylase expression in catecholaminergic central and peripheral nervous system cell lines from transgenic mice.J Biol Chem 270, no. 37 (September 15, 1995): 21579–89. https://doi.org/10.1074/jbc.270.37.21579.
Lazaroff, M., et al. “The cyclic AMP response element directs tyrosine hydroxylase expression in catecholaminergic central and peripheral nervous system cell lines from transgenic mice.J Biol Chem, vol. 270, no. 37, Sept. 1995, pp. 21579–89. Pubmed, doi:10.1074/jbc.270.37.21579.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

September 15, 1995

Volume

270

Issue

37

Start / End Page

21579 / 21589

Location

United States

Related Subject Headings

  • Tyrosine 3-Monooxygenase
  • Transfection
  • Transcription, Genetic
  • Restriction Mapping
  • Recombinant Proteins
  • Rats
  • Promoter Regions, Genetic
  • Peripheral Nerves
  • Mutagenesis
  • Molecular Sequence Data