Identification of a photoreceptor cell-specific nuclear receptor

Nuclear receptors comprise a large and expanding family of transcription fa ctors involved in diverse aspects of animal physiology and development, the functions of which can be modulated in a spatial and temporal manner by ac cess to small lipophilic ligands and/or the specificity of their own locali zed expression. Here we report the identification of a human nuclear recept or that reveals a unique proximal box (CNGCSG) in the DNA-binding domain. T he conservation of this feature in its nematode counterpart suggests the re quirement for this type of P box in the genetic cascades mediated by nuclea r receptors in a wide variety of animal species. The expression of this rec eptor, PNR (photoreceptor-specific nuclear receptor), appears strongly rest ricted in the retina, exclusively in photoreceptor cells. In human cell lin es, PNR expression was observed in Y79 retinoblastoma along with other phot oreceptor marker genes such as CRX, Among vertebrate receptors, PNR shares structural kinship with an orphan receptor TLX, and despite distinct differ ences in the DNA binding domain, PNR is able to recognize a subset of TLX t arget sequences in vitro, Analyses of the human PNR gene revealed its chrom osomal position as 15q24, a site that has recently been reported as a susce ptible region for retinal degeneration. These data support a role for PNR i n the regulation of signalling pathways intrinsic to the photoreceptor cell function.