Sp4 is expressed in retinal neurons, activates transcription of photoreceptor-specific genes, and synergizes with Crx

Leonid E. Lerner, Guang Hua Peng, Yekaterina E. Gribanova, Shiming Chen, Debora B. Farber

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

To investigate the molecular mechanisms of photoreceptor-specific gene transcription, we examined the role of the neuronal-enriched Sp4 nuclear protein in transcription from the rod-specific β-PDE and rod opsin gene promoters and compared it to the ubiquitous members of the Sp family, Sp1 and Sp3. Sp4 activates both the rod opsin and β-PDE promoters, whereas Sp1 activates only the rod opsin promoter and Sp3 activates neither promoter. Interestingly, Sp1 and Sp3 competitively repress Sp4-mediated activation of the β-PDE promoter. In addition, Sp4, Sp1, and Sp3 each show functional synergy with the photoreceptor-enriched Crx transcriptional regulator on the rod opsin promoter but not the β-PDE promoter, although Sp4-mediated activation was the most significant. Sp4, Sp1, and Sp3 bind Crx in co-immunoprecipitation experiments, and their zinc finger domains as well as the Crx homedomain are necessary and sufficient for these interactions. Chromatin immunoprecipitation showed that the rod opsin and β-PDE promoters are targets of both Sp4 and Crx, which further supports Sp4-Crx interactions in vivo in the context of retinal chromatin environment. In situ hybridization and immunohistochemistry demonstrated that Sp4 is abundantly expressed in various neurons of all retinal layers, and thus co-localizes or overlaps with multiple retina-restricted and -enriched genes, its putative targets. Our results indicate that photoreceptor-specific gene transcription is controlled by the combinatorial action of Sp4 and Crx. The other Sp family members may be involved in photoreceptor-specific transcription directly or through their competition with Sp4. These data suggest the potential importance of Sp4 in retinal neurobiology and pathology.

Original languageEnglish
Pages (from-to)20642-20650
Number of pages9
JournalJournal of Biological Chemistry
Volume280
Issue number21
DOIs
StatePublished - May 27 2005

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