Direct evidence that the POU family transcription factor Oct-2 represses the cellular tyrosine hydroxylase gene in neuronal cells.
The POU family transcription factor Oct-2 was originally identified in B lymphocytes but has been shown to be expressed in neuronal cells, although it is absent in most other cell types. Cotransfection of Oct-2 expression vectors into nonneuronal cells with a tyrosine hydroxylase promoter/reporter plasmid suggests that Oct-2 can repress this promoter in this artificial situation. Here we report that reduction of endogenous Oct-2 levels in a neuronal cell line by an antisense approach results in an increase in endogenous tyrosine hydroxylase levels. In contrast, the level of the neuronal marker protein PGP9.5 remains unchanged in the antisense lines whereas that of the neuronal nitric oxide synthase decreases. Hence, the tyrosine hydroxylase gene is a natural target for repression by Oct-2 in neuronal cells. The significance of this effect is discussed in terms of the processes that regulate tyrosine hydroxylase gene expression and the role of Oct-2 in neuronal cells.
Deans
Z
Z
Department of Molecular Pathology, University College London Medical School, UK.
Dawson
S J
SJ
Buttery
L
L
Polak
J M
JM
Wallace
D
D
Latchman
D S
DS
D000818:Animals; D016375:Antisense Elements (Genetics); D001483:Base Sequence; D015415:Biomarkers; D015153:Blotting, Western; D002460:Cell Line / Q000201:enzymology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D007150:Immunohistochemistry; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000201:enzymology*; D050813:Octamer Transcription Factor-2; D050809:POU Domain Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D016375:Antisense Elements (Genetics); D015415:Biomarkers; D004268:DNA-Binding Proteins; D050813:Octamer Transcription Factor-2; D050809:POU Domain Factors; C489206:Pou2f2 protein, mouse; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase