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L.E. Lerner, Y. Gribanova, D.B. Farber; Transcription Factors of the Sp Family Synergize With Both Nrl and Crx, and Regulate the Expression of Multiple Retina-Specific Genes . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3535.
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Purpose: The Sp1 and Sp4 transcription factors have been implicated in transcriptional control of a number of genes in various tissues. Although Sp1 is ubiquitously expressed, Sp4 is predominantly expressed in CNS, including the retina. Transcription factors Nrl and Crx are essential for the expression of a number of photoreceptor-specific genes during development and in the adult retina. We reported previously that Sp4 and Nrl, but not Crx had major roles in transcriptional activation of the rod cGMP-phophodiesterase ß-subunit (ß-PDE) promoter. The purpose of this study was to test whether these transcription factors are able to functionally interact with each other on different promoters providing a novel mechanism for combinatorial regulation of multiple retina-specific genes. Methods: Transient transfection and co-transfection assays were performed in 293 human embryonic kidney (293HEK) cells. Luciferase reporter constructs containing promoters from Rhodopsin, Arrestin, IRBP, RPE65, or α’-PDE genes were employed. In order to test the mutual functional effects of the transcription factors of interest, expression plasmids encoding Sp1, Sp4, Nrl or Crx were added to transfection mixtures individually or in combinations. Results: Both Sp1 and Sp4 were able to activate promoter activity of multiple retina-specific genes. The Sp4-mediated activation was generally more pronounced than that by Sp1. Both Sp1 and Sp4 showed synergistic effects with Nrl or Crx suggesting the possibility of functional interactions between these transcription factors in vivo. Conclusions: These results suggest that Sp1 and Sp4 could regulate the expression of multiple retinal genes in combinatorial fashion by interacting with other transcription factors including Nrl and Crx.
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