|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0017337,
umls-concept:C0018338,
umls-concept:C0031640,
umls-concept:C0040649,
umls-concept:C0086860,
umls-concept:C0205245,
umls-concept:C0206427,
umls-concept:C0441655,
umls-concept:C0936012,
umls-concept:C1514873,
umls-concept:C1546857,
umls-concept:C1556066,
umls-concept:C1619636
|
|
pubmed:issue |
19
|
|
pubmed:dateCreated |
2004-5-4
|
|
pubmed:abstractText |
To understand the factors controlling expression of the cGMP phosphodiesterase type 6 (PDE6) genes, we have characterized the promoter of the human PDE6A gene that encodes the catalytic alpha-subunit. In vivo DNase I hypersensitivity assays revealed two sites immediately upstream of the PDE6A core promoter region. Transient transfection assay in Y79 cells of constructs containing varying lengths of the promoter region showed a decrease in promoter activity with increasing length. The most active segment contained a 177-bp upstream sequence including apparent Crx and Nrl transcription factor binding sites. Both Crx and Nrl transactivated the PDE6A promoter in HEK293 cells and showed a >100-fold increase when coexpressed. Coexpression of a dominant negative inhibitor of Nrl abolished Nrl transactivation but had no effect on Crx. DNase I footprinting assays identified three potential Crx binding sites within a 55-bp segment beginning 29 bp upstream of the transcription start point. Mutation of two of these sites reduced reporter gene activity by as much as 69%. Gel shifts showed that all three Crx sites required a TAAT sequence for efficient binding. Consistent with a requirement for Crx and Nrl in Pde6a promoter activity, Pde6a mRNA is reduced by 87% in the retina of Crx(-/-) mice and is undetectable in Nrl(-/-) mice at postnatal day 10. These results establish that both Nrl and Crx are required for full transcriptional activity of the PDE6A gene.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3',5'-Cyclic-GMP Phosphodiesterases,
http://linkedlifedata.com/resource/pubmed/chemical/Basic-Leucine Zipper Transcription...,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Phosphates,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic Nucleotide...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyribonuclease I,
http://linkedlifedata.com/resource/pubmed/chemical/Eye Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/NRL protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nrl protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/PDE6A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Pde6a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Galactosidase,
http://linkedlifedata.com/resource/pubmed/chemical/calcium phosphate,
http://linkedlifedata.com/resource/pubmed/chemical/cone rod homeobox protein
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
May
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
7
|
|
pubmed:volume |
279
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
19800-7
|
|
pubmed:dateRevised |
2008-11-21
|
|
pubmed:meshHeading |
pubmed-meshheading:15001570-Humans,
pubmed-meshheading:15001570-Animals,
pubmed-meshheading:15001570-Mice,
pubmed-meshheading:15001570-Calcium Phosphates,
pubmed-meshheading:15001570-Retina,
pubmed-meshheading:15001570-Mutation,
pubmed-meshheading:15001570-Luciferases,
pubmed-meshheading:15001570-DNA,
pubmed-meshheading:15001570-Deoxyribonuclease I,
pubmed-meshheading:15001570-Cell Nucleus,
pubmed-meshheading:15001570-Adenoviridae,
pubmed-meshheading:15001570-Base Sequence,
pubmed-meshheading:15001570-Time Factors,
pubmed-meshheading:15001570-Eye Proteins,
pubmed-meshheading:15001570-Protein Binding,
pubmed-meshheading:15001570-Genes, Dominant,
pubmed-meshheading:15001570-Binding Sites,
pubmed-meshheading:15001570-Cell Line,
pubmed-meshheading:15001570-beta-Galactosidase,
pubmed-meshheading:15001570-Dose-Response Relationship, Drug,
pubmed-meshheading:15001570-Molecular Sequence Data,
pubmed-meshheading:15001570-Transcription, Genetic,
pubmed-meshheading:15001570-Cloning, Molecular,
pubmed-meshheading:15001570-Retinal Rod Photoreceptor Cells,
pubmed-meshheading:15001570-Plasmids,
pubmed-meshheading:15001570-Promoter Regions, Genetic,
pubmed-meshheading:15001570-DNA-Binding Proteins,
pubmed-meshheading:15001570-Glutathione Transferase,
pubmed-meshheading:15001570-Transfection,
pubmed-meshheading:15001570-Transcriptional Activation,
pubmed-meshheading:15001570-3',5'-Cyclic-GMP Phosphodiesterases,
pubmed-meshheading:15001570-Trans-Activators,
pubmed-meshheading:15001570-Mice, Knockout,
pubmed-meshheading:15001570-DNA Mutational Analysis
|
