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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