Abstract
Selective expression of retinal cone opsin genes is essential for color vision, but the mechanism mediating this process is poorly understood. Both vertebrate rod and medium wavelength–sensitive (M) cone photoreceptors differentiate by repression of a short wavelength–sensitive (S) cone differentiation program. We found that Pias3 acts in mouse cone photoreceptors to activate expression of M opsin and repress expression of S opsin, with the transcription factors Trβ2 and Rxrγ mediating preferential expression of Pias3 in M cones. Finally, we observed that Pias3 directly regulated M and S cone opsin expression by modulating the cone-enriched transcription factors Rxrγ, Rorα and Trβ1. Our results indicate that Pias3-dependent SUMOylation of photoreceptor-specific transcription factors is a common mechanism that controls both rod and cone photoreceptor subtype specification, regulating distinct molecular targets in the two cell types.
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Acknowledgements
We thank D. Forrest for providing antibodies to Trβ2 and for supplying Trβ2−/− and Trβ1−/−; Trβ2−/− mice. We also thank J. Nathans, T. Shimogori, W. Yap and members of the Blackshaw laboratory for their comments on the manuscript. This work was supported by grants from the US National Institutes of Health (R01EY017015 to S.B. and RO1EY012543 to S.C.). S.B. is a W.M. Keck Distinguished Young Investigator in Medical Science.
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A.O., S.C. and S.B. designed the study. A.O. and G.-H.P. performed the experiments. A.O., G.-H.P. and S.C. contributed reagents and analytic tools. A.O., G.-H.P., S.C. and S.B. analyzed the data. A.O. and S.B. wrote the manuscript.
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Onishi, A., Peng, GH., Chen, S. et al. Pias3-dependent SUMOylation controls mammalian cone photoreceptor differentiation. Nat Neurosci 13, 1059–1065 (2010). https://doi.org/10.1038/nn.2618
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DOI: https://doi.org/10.1038/nn.2618
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