An AP-2 binding sequence within exon 1 of human and porcine choline acetyltransferase genes enhances transcription in neural cells

F. Baskin, Y. P. Li, L. B. Hersh, R. M. Davis, R. N. Rosenberg

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The gene for choline acetyltransferase, synthesizing acetylcholine, is induced by several neurotrophic factors. A role for AP-2 in enhancing this transcription and limiting it to neural cells is strongly suggested. Previous studies demonstrated that base pairs +465-727 within the untranslated exon 1 of the porcine gene enhanced the expression of a reporter gene transfected into PC-12 cells. Deletion and mutation experiments indicate that base pairs +465-472 (CCGCGGGG) in the porcine gene, or +307-314 (CCTCGGGG) in the human sequence, were necessary and sufficient for increased gene expression in cholinergic or adrenergic but not liver cells. Constructs containing active sequences, but not inactive mutated sequences, specifically bind nuclear proteins from neuroblastoma cells, but not liver cells, in gel shift experiments. The human and porcine sequences are in agreement with an AP-2 consensus binding sequence, a nuclear transcription factor expressed only in cells derived from the neural crest. Gel shift experiments using recombinant AP-2 confirm this identification. AP-2 antibody further retarded the mobility of these DNA-nuclear extract or DNA-AP-2 complexes. These results support the importance of this AP-2 binding sequence in enhancing and limiting choline acetyltransferase expression in neural cells.

Original languageEnglish (US)
Pages (from-to)821-827
Number of pages7
JournalNeuroscience
Volume76
Issue number3
DOIs
StatePublished - Dec 11 1996

Fingerprint

Choline O-Acetyltransferase
Exons
Swine
Genes
Base Pairing
Gels
Gene Expression
Neural Crest
Sequence Deletion
Liver
DNA
Consensus Sequence
Nerve Growth Factors
Nuclear Proteins
Neuroblastoma
Reporter Genes
Adrenergic Agents
Cholinergic Agents
Acetylcholine
Transcription Factors

Keywords

  • AP-1
  • cholinergic expression
  • enhancer element
  • gene regulation
  • gene transcription
  • SP1

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

An AP-2 binding sequence within exon 1 of human and porcine choline acetyltransferase genes enhances transcription in neural cells. / Baskin, F.; Li, Y. P.; Hersh, L. B.; Davis, R. M.; Rosenberg, R. N.

In: Neuroscience, Vol. 76, No. 3, 11.12.1996, p. 821-827.

Research output: Contribution to journalArticle

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