Differential regulation of the two neuronal nitric-oxide synthase gene promoters by the Oct-2 transcription factor.
The Oct-2 transcription factor has been shown previously to repress both the cellular tyrosine hydroxylase and the herpes simplex virus immediate-early genes in neuronal cells. Here we identify the gene encoding the neuronal nitric-oxide synthase (nNOS) as the first example of a gene activated in neuronal cells by Oct-2. The levels of the nNOS mRNA and protein are greatly reduced in neuronal cell lines in which Oct-2 levels have been reduced by an antisense method, although these cells have enhanced levels of tyrosine hydroxylase. Moreover, the nNOS gene regulatory region is activated by Oct-2 expression vectors upon cotransfection into both neuronal and non-neuronal cells, and this response is dependent upon a 20-amino acid region within the COOH-terminal activation domain of Oct-2. Of the two closely linked promoters that drive nNOS gene expression, only the downstream 5.1 promoter is activated by Oct-2, whereas the 5.2 promoter is unaffected. These effects are discussed in terms of the potential role of Oct-2 in regulating nNOS expression in the nervous system.
Deans
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Department of Molecular Pathology, University College London Medical School, London W1P 6DB, United Kingdom. j.wenley@ucl.ac.uk
Dawson
S J
SJ
Xie
J
J
Young
A P
AP
Wallace
D
D
Latchman
D S
DS
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000494:pharmacology*
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D019001:Nitric Oxide Synthase