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R. S. Mali, X. M. Zhang, K. P. Mitton; FIZ1 Supports Transcriptional Synergy With NRL at Rod Specific Promoters and Intensifies the Effect of NRLS50T in vitro. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2922.
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© ARVO (1962-2015); The Authors (2016-present)
FIZ1 is a multiple zinc finger protein that can interact with NRL to increase its activation of the rod-specific gene promoters, Rho and PDE6B, in vitro. To examine the domain-function relationships in FIZ1, deletion constructs were tested using yeast two-hybrid interaction assays and transient co-transfection of CV1 cells. FIZ1 activation synergy with NRL and NRLS50T (AD-RP) were compared at the Rho and PDE6B promoters.
Protein interactions were examined with yeast two hybrid assays and functional tests were carried out using co-transfection promoter-activation assays.
The C-terminal zinc fingers (ZF 9-11) of FIZ1 were necessary and sufficient to interact with NRL; however, they were necessary but insufficient for activation synergy of the minimal Rho and PDE6B test promoters. NRLS50T was a stronger activator of the Rho and PDE6B gene promoters compared to wild type NRL. The magnitude of this difference was increased substantially in the presence of FIZ1.
Our results support the hypothesis that FIZ1 has a role to support the NRL-mediated expression of maturation-related genes, such as Rho and PDE6B in retinal development. The hyper-activation effect of NRLS50T was magnified in the presence of FIZ1.
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