title: A 350 bp region of the proximal promoter of Rds drives cell-type specific gene expression.
abstract: RDS (retinal degeneration slow) is a photoreceptor-specific tetraspanin protein required for the biogenesis and maintenance of rod and cone outer segments. Mutations in the Rds gene are associated with multiple forms of rod- and cone-dominant retinal degeneration. To gain more insight into the mechanisms underlying the regulation of this gene, the identification of regulatory sequences within the promoter of Rds was undertaken. A 3.5 kb fragment of the 5' flanking region of the mouse Rds gene was isolated and binding sites for Crx, Otx2, Nr2e3, RXR family members, Mef2C, Esrrb, NF1, AP1, and SP1 in addition to several E-boxes, GC-boxes and GAGA-boxes were identified. Crx binding sequences were conserved in all mammalian species examined. Truncation expression analysis of the Rds promoter region in Y-79 retinoblastoma cells showed maximal activity in the 350 bp proximal promoter region. We also show that inclusion of more distal fragments reduced promoter activity to the basal level, and that the promoter activities are cell-type and direction specific. Co-transfection with Nrl increased promoter activity, suggesting that this gene positively regulates Rds expression. Based on these findings, a relatively small fragment of the Rds promoter may be useful in future gene transfer studies to drive gene expression in photoreceptors.
authors.affiliation: Department of Cell Biology, University Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd, BMSB 781, Oklahoma City, OK 73104, USA.
authors.forename: Xue
authors.initials: X
authors.lastname: Cai
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Conley
authors.forename: Tong
authors.initials: T
authors.lastname: Cheng
authors.forename: Muayyad R
authors.initials: MR
authors.lastname: Al-Ubaidi
authors.forename: Muna I
authors.initials: MI
authors.lastname: Naash
mesh_terms: D024506:5' Flanking Region / Q000235:genetics; D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D003001:Cloning, Molecular; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation / Q000502:physiology*; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics*; D064531:Peripherins; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000235:genetics*; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics; D012162:Retinal Degeneration / Q000235:genetics*; D019572:Retinal Neoplasms / Q000235:genetics; D012175:Retinoblastoma / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D064531:Peripherins; C578996:Prph2 protein, mouse; D038621:Regulatory Sequences, Ribonucleic Acid; D014157:Transcription Factors
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