Transcription of photoreceptor genes during fetal retinal development. Evidence for positive and negative regulation

Rod photoreceptor outer segments are elaborated at approximately 6 months gestation in the cow coinciding with a dramatic increase in mRNAs encoding many visual transduction and associated proteins. Nuclear run-on determination of relative transcription rates demonstrates that gene expression follows three distinct patterns. Opsin, S-antigen, and transducin are all minimally detectable at 5.2 months gestation and increase throughout development. Only opsin demonstrates an additional sharp increase in transcriptional activity which resembles a positive gene-specific enhancer that is first effective between 6.3 and 7.4 months gestation. In contrast, interphotoreceptor retinoid binding protein (IRBP) transcription is already at 43% of its adult level at 5.2 months gestation. To further understand these differences, the relative contributions of initiation and elongation to nuclear run-on signals were examined using either Sarkosyl or ammonium sulfate. Transcriptional rates for S-antigen and transducin were not affected, however, opsin was reduced approximately 4-fold and IRBP was increased approximately 2-fold. Opsin is therefore likely to be initiated de novo during the run-on reaction and responds to a gene-specific positive regulator. The increase in IRBP transcription rate suggests the removal of an elongation inhibitory factor and supports the idea that a negative regulatory element may be involved in controlling IRBP expression.