Conserved interactions of a compact highly active enhancer/promoter upstream of the rhodopsin kinase (GRK1) gene.
Rhodopsin kinase (RK) is a conserved component of the light adaptation and recovery pathways shared among rod and cone photoreceptors of a variety of species. To gain insight into transcriptional mechanisms driving RK and potentially other genes of similar spatial profile, the components and the interactions of the highly compact enhancer/promoter region (E/P) upstream of the human RK gene were examined. Cross-species comparison outlined an active 49-bp widely shared E/P core as the major site of conservation in the entire 5' flanking sequence. The area consisted of a bicoid-type homeodomain recognition cassette and a unique T-rich module interacting with TATA-binding proteins. Homeodomain interactions involved primarily Crx and secondarily Otx2. Both strongly stimulated the E/P. In the absence of Crx, persistent E/P activity shifted from the outer retina to the inner to follow the Otx2 pattern. The spatial patterns were largely unaffected by the absence of rod transcription factors, Nrl and Nr2e3, and the RK transcriptional activity preceded the surge in rod-specific transcription. Conserved bicoid homeodomain factors thus appear to be the key factors governing localization of RK E/P activity in retina and photoreceptors.
Young
Joyce E
JE
Department of Ophthalmology, Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY 14215, USA.
Kasperek
Eileen M
EM
Vogt
Todd M
TM
Lis
Agnieszka
A
Khani
Shahrokh C
SC
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002478:Cells, Cultured; D017124:Conserved Sequence; D004742:Enhancer Elements, Genetic; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D051857:Otx Transcription Factors / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012160:Retina / Q000378:metabolism; D035181:TATA-Box Binding Protein / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D018398:Homeodomain Proteins; D051857:Otx Transcription Factors; D035181:TATA-Box Binding Protein; C509817:TBP protein, human; D015534:Trans-Activators; C109288:cone rod homeobox protein; D051606:G-Protein-Coupled Receptor Kinase 1