Deans, Zandra Crozier; (1997) Regulation of neuronal gene expression by Oct 2. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Oct 2 is a POU-protein which is expressed in sensory neurons but whose cellular function has not yet been identified. In order to identify Oct 2 regulated neuronal genes, antisense Oct 2 sensory neuronal cell lines were created. Two antisense Oct 2 cell lines showed reduced levels of Oct 2 protein. The tyrosine hydroxylase promoter has previously been shown to be regulated by Oct 2. Immunocytochemistry, immunoblotting and RT-PCR identified an upregulation in endogenous tyrosine hydroxylase mRNA and protein expression in the antisense Oct 2 cell lines when compared with the parental ND7 cell line. The synaptic vesicle proteins, SNAP-25 and synapsin I showed increased protein expression in these cell lines and Oct 2 mediated repression of the synapsin I gene promoter was demonstrated. Neuronal nitric oxide synthase mRNA and protein expression was shown to be down regulated in the antisense Oct 2 cell lines when compared with the parental ND7 cell line. The full length 4.3 kilobase nNOS gene promoter was shown to be the first naturally occurring neuronal promoter to be activated by Oct 2. This Oct 2 regulation was shown to be specific to the 5'1 nNOS gene promoter. Oct 2.1 activation of the 4.3 kilobase nNOS promoter and the 5'1 specific nNOS promoter is mediated by the Oct 2 C-terminal activation domain. The Oct 2.4 and Oct 2.5 isoforms activate both these promoters in neuronal cells but do not contain this functional domain. These Oct 2 isoforms appear to activate the nNOS promoters via an interaction with a neuronal-specific factor expressed in ND7 cells mediated by the Oct 2 protein N-terminus region.

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