Purchase this article with an account.
S. Chen, G.–H. Peng, J. Liu; The Homeodomain Transcription Factor Otx2 Binds to the Regulatory Region of Photoreceptor Genes and Partially Compensates for Crx Deficiency in Crx–/– Mice . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2395.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: The transcription factor Otx2 is essential for brain and sense organ development. In developing photoreceptors, expression of Otx2 induces another Otx family member, Crx, which is required for terminal differentiation and maintenance of photoreceptors. Crx and Otx2 share a conserved homeodomain and recognize similar DNA motifs in vitro. This study was performed to identify additional photoreceptor genes regulated by Otx2 and investigate its role in target gene transcription. Methods: Chromatin immunoprecipitation (ChIP) was performed on postnatal day 14 retinas of wild–type and Crx–/– mice using an anti–Otx2 antibody (which cross–reacts with Crx). Otx2–immunoprecipitated chromatin was analyzed by PCR with primers specific to regulatory regions of candidate photoreceptor genes. Co–transfection assays in HEK293 cells were then performed to confirm the ability of Otx2 to regulate transcription of the implicated genes. Results:Otx2 (and Crx) occupies the promoter/enhancer region of both Crx–dependent (rhodopsin, M– and S–cone opsin and Pde6b) and independent (Irbp and rhodopsin kinase) photoreceptor genes. Otx2 binding to these targets was confirmed by ChIP using Crx–/– mice. Expression of the Otx2 protein in HEK293 cells produced a low but consistent regulatory activity on luciferase reporters driven by several target gene promoters. However, this regulatory activity is much lower than that of Crx. Furthermore, Otx2 does not synergize with Nrl to the same degree as Crx. Our results and previously reported up–regulation of Otx2 in Crx–/– mice are consistent with the fact that the expression of many photoreceptor genes is reduced (or unaffected) but not abolished by Crx deficiency. Conclusions: Otx2 plays a redundant but differential role with Crx in regulating the expression of many photoreceptor genes. Due to a low potency, Otx2 can only partially compensate for Crx function in Crx–/– mice. This study provides new information on the mechanism for photoreceptor–specific gene expression.
This PDF is available to Subscribers Only