Both PCE-1/RX and OTX/CRX interactions are necessary for photoreceptor-specific gene expression.
RX, a homeodomain-containing protein essential for proper eye development (Mathers, P. H. Grinberg, A., Mahon, K. A., and Jamrich, M. (1997) Nature 387, 603-607), binds to the photoreceptor conserved element-1 (PCE-1/Ret 1) in the photoreceptor cell-specific arrestin promoter and stimulates gene expression. RX is found in many retinal cell types including photoreceptor cells. Another homeodomain-containing protein, CRX, which binds to the OTX element to stimulate promoter activity, is found exclusively in photoreceptor cells (Chen, S., Wang, Q. L., Nie, Z., Sun, H., Lennon, G., Copeland, N. G., Gillbert, D. J. Jenkins, N. A., and Zack, D. J. (1997) Neuron 19, 1017-1030; Furukawa, T., Morrow, E. M., and Cepko, C. L. (1997) Cell 91, 531-541). Binding assay and cell culture studies indicate that both PCE-1 and OTX elements and at least two different regulatory factors RX and CRX are necessary for high level, photoreceptor cell-restricted gene expression. Thus, photoreceptor specificity can be achieved by multiple promoter elements interacting with a combination of both photoreceptor-specific regulatory factors and factors present in closely related cell lineages.
Kimura
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A
Center for Ophthalmic Research, Brigham & Women's Hospital, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Singh
D
D
Wawrousek
E F
EF
Kikuchi
M
M
Nakamura
M
M
Shinohara
T
T
D000595:Amino Acid Sequence; D000818:Animals; D019393:Arrestin / Q000235:genetics*; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002417:Cattle; D002645:Chickens; D017124:Conserved Sequence; D005136:Eye Proteins; D005786:Gene Expression Regulation; D015723:Gene Library; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007438:Introns; D007498:Iris / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012160:Retina / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D015533:Transcriptional Activation
D019393:Arrestin; D005136:Eye Proteins; D018398:Homeodomain Proteins; D015345:Oligonucleotide Probes; C486393:RAX protein, human; C105441:Rax protein, mouse; D011993:Recombinant Fusion Proteins; C111251:Rx protein, vertebrate; D015534:Trans-Activators; D014157:Transcription Factors; C109288:cone rod homeobox protein