FIZ1 is part of the regulatory protein complex on active photoreceptor-specific gene promoters in vivo.

Publisher: BioMed Central Country of Publication: England NLM ID: 100966983 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2199 (Electronic) Linking ISSN: 14712199 NLM ISO Abbreviation: BMC Mol Biol Subsets: MEDLINE

Original Publication: London : BioMed Central, [2000]-[2019]

Promoter Regions, Genetic*; Intracellular Signaling Peptides and Proteins/*metabolism ; Photoreceptor Cells, Vertebrate/*physiology; Animals ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Homeodomain Proteins/physiology ; Intracellular Signaling Peptides and Proteins/genetics ; Mice ; Neurons/metabolism ; Neurons/ultrastructure ; Photoreceptor Cells, Vertebrate/metabolism ; Photoreceptor Cells, Vertebrate/ultrastructure ; Recombinant Proteins/metabolism ; Retina/cytology ; Retina/metabolism ; Trans-Activators/genetics ; Trans-Activators/metabolism ; Trans-Activators/physiology

Background: FIZ1 (Flt-3 Interacting Zinc-finger) is a broadly expressed protein of unknown function. We reported previously that in the mammalian retina, FIZ1 interacts with NRL (Neural-Retina Leucine-zipper), an essential transcriptional activator of rod photoreceptor-specific genes. The concentration of FIZ1 in the retina increases during photoreceptor terminal maturation, when two key transcription factors NRL and CRX (Cone-Rod Homeobox) become detectable on the promoters of photoreceptor-specific genes (i.e. Rhodopsin, Pde6b). To determine if FIZ1 is involved in regulating CRX-mediated transcriptional activation, we examined FIZ1 subcellular location in mouse neural retina, its ability to interact with CRX, and its association with CRX/NRL target genes.
Results: FIZ1 is present in the nucleus of adult photoreceptors as well as other retinal neurons as shown by transmission electron microscopy with nano-gold labeling. FIZ1 and CRX were co-precipitated from retinal nuclear extracts with antibodies to either protein. Chromatin immunoprecipitation (ChIP) assays revealed that FIZ1 is part of the protein complex on several rod and cone gene promoters, within photoreceptor cells of the mouse retina. FIZ1 complexes with CRX or NRL on known NRL- and CRX-responsive elements, as shown by electrophoretic mobility shift assays with FIZ1 antibody. FIZ1 can directly bind to CRX, as demonstrated using yeast two-hybrid and GST pull-down assays. Co-transfection assays demonstrated that FIZ1 increases CRX-mediated activation of Opsin test promoters. Quantitative ChIP analysis revealed an increased association of FIZ1 with the Rhodopsin promoter in adult (P-25) neural retina versus immature (P-3) neural retina. The quantity of transcriptionally active RNA Polymerase-II within the Rhodopsin gene (Rho) was significantly increased in the adult neural retina, compared to the immature retina.
Conclusion: FIZ1 directly interacts with CRX to enhance CRX's transactivation activity for target genes. Developmentally, in neural retina tissue, the increased association of FIZ1 with CRX target genes corresponds to an increased association of transcriptionally active Pol-II within the Rho gene. Together with previous findings, our results suggest that FIZ1 may act as a transcriptional co-regulator of photoreceptor-specific genes, recruited by at least two photoreceptor-specific transcription factors, CRX and NRL. Further studies are underway to elucidate the exact role of FIZ1 in photoreceptor gene expression, development and maintenance.

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R01 EY014626 United States EY NEI NIH HHS; EY012543 United States EY NEI NIH HHS; R01 EY012543-08 United States EY NEI NIH HHS; R24 EY014803 United States EY NEI NIH HHS; R01 EY012543 United States EY NEI NIH HHS; R01 EY012543-09 United States EY NEI NIH HHS; EY014626 United States EY NEI NIH HHS; EY014803 United States EY NEI NIH HHS

0 (Fiz1 protein, mouse)
0 (Homeodomain Proteins)
0 (Intracellular Signaling Peptides and Proteins)
0 (Recombinant Proteins)
0 (Trans-Activators)
0 (cone rod homeobox protein)

Date Created: 20081016 Date Completed: 20081112 Latest Revision: 20181113

20231215

PMC2571102

10.1186/1471-2199-9-87

18854042