May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
FIZ1 Supports Transcriptional Synergy With NRL at Rod Specific Promoters and Intensifies the Effect of NRLS50T in vitro
Author Affiliations & Notes
  • R. S. Mali
    Eye Research Institute, Oakland University, Rochester, Michigan
  • X. M. Zhang
    Eye Research Institute, Oakland University, Rochester, Michigan
  • K. P. Mitton
    Eye Research Institute, Oakland University, Rochester, Michigan
  • Footnotes
    Commercial Relationships R.S. Mali, None; X.M. Zhang, None; K.P. Mitton, None.
  • Footnotes
    Support NIH Grant EY 014626 (Mitton), EY 014803 (ERI/Oakland University)
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 2922. doi:
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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)

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Abstract

Purpose:: 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.

Methods:: Protein interactions were examined with yeast two hybrid assays and functional tests were carried out using co-transfection promoter-activation assays.

Results:: 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.

Conclusions:: 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.

Keywords: retinal development • gene/expression • transcription factors 
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