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K. P. Mitton, R. S. Mali, X. M. Zhang; Fiz1 as a Maturation Factor in Neural Retina That Binds to Photoreceptor-Specific Transcription Factors and Supports Transcription of Maturation-Related Genes. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2921.
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Several photoreceptor-specific transcription factors are present in photoreceptor precursors prior to the expression of maturation-related genes under their control. We do not fully understand why these transcription factors eventually activate these genes as maturation begins. FIZ1 is a multiple zinc finger protein whose expression increases dramatically in the neural retina during the maturation phase. We tested FIZ1 for interactions with these transcription factors and examined the effects of FIZ1 on the activation of several photoreceptor-specific gene promoters.
Protein interactions were examined with yeast-two hybrid and GST pull-down assays. Co-transfection promoter-activation assays were carried out with luciferase reporter plasmids containing minimal Rho, PDE6B, M-opsin and S-opsin promoters.
In addition to the known interaction of FIZ1 with NRL, FIZ1 could also bind to the CRX transcription factor as determined by both yeast two-hybrid and GST pull down assays. Promoter-activation assays demonstrated that FIZ1 interaction could produce transcriptional synergy with NRL at the Rho and PDE6B minimal promoters. Furthermore, FIZ1 synergized with CRX to activate the M- and S-opsin promoters.
Several results suggest that FIZ1 could be a factor that promotes the expression of maturation-related genes in retinal development. These include: the timing of FIZ1 expression in the mouse neural retina, its ability to bind to NRL and CRX, and FIZ1's ability to synergize with these transcription factors at both rod and cone-specific promoters.
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