Human gene encoding prostacyclin synthase (PTGIS): Genomic organization, chromosomal localization, and promoter activity
- National Cardiovascular Center Research Institute, Osaka (Japan); and others
The prostacyclin synthase gene isolated from human genomic libraries (PTGIS) consists of 10 exons spanning approximately 60 kb. All the splice donor and acceptor sites conform to the GT/AG rule. Genomic Southern blot and fluorescence in situ hybridization analyses revealed that the human prostacyclin synthase gene is present as a single copy per haploid genome and is localized on chromosome 20q13.11-q13.13. The 1.5-kb sequence of the 5{prime} of the translational initiation site contained both GC-rich and pyrimidine-rich regions and consensus sequences of the transcription factor recognition sites such as Sp1, AP-2, the interferon-{gamma} response element, GATA, NF-{kappa}B, the CACCC box, and the glucocorticoid response element. The core binding sequence (GAGACC) of the shear stress responsive element was also found in the 5{prime}-flanking region of the gene. The major product of the primer extension analysis suggested that the transcription of the gene started from the positions around 49 bp upstream of the translational initiation codon. Transient transfection experiments using human aortic and bovine arterial endothelial cells demonstrated that the GC-rich region (positions -145 to -10) possessed a significant promoter activity. The 6-kb downstream sequence of the translational termination codon contained multiple polyadenylation signals, Alu repeat sequences, and the consensus sequence of the primate-repetitive DNA element, MER1. Two sizes of the prostacyclin synthase mRNAs (approximately 6 and 3.3 kb) were detected with the human aorta and lung. RNA blot hybridization analysis using the 3{prime}-untranslated region as probe indicated that the sizes of the 3{prime}-flanking regions were different in the major 6-kb and minor 3.3-kb mRNAs. 54 refs., 7 figs.
- OSTI ID:
- 486315
- Journal Information:
- Genomics, Vol. 36, Issue 2; Other Information: PBD: 1 Sep 1996
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
GENES
STRUCTURE-ACTIVITY RELATIONSHIPS
DNA SEQUENCING
GENETIC MAPPING
TRANSCRIPTION
SPLICING
GENE REGULATION
DNA-CLONING
HUMAN CHROMOSOMES
HAPLOIDY
TRANSCRIPTION FACTORS
EXONS
INTRONS
DNA HYBRIDIZATION
FLUORESCENCE
CODONS
MESSENGER-RNA
PROSTAGLANDINS
NUCLEOTIDES
ENZYMES