Human plasminogen activator inhibitor-1 gene. Promoter and structural gene nucleotide sequences

• Published in: The Journal of biological chemistry 1988-07, Vol.263 (19), p.9129-9141
• Main Authors: Bosma, P J, van den Berg, E A, Kooistra, T, Siemieniak, D R, Slightom, J L
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; Biological and medical sciences; Biotechnology; Cloning, Molecular; Cosmids; Exons; Female; Fundamental and applied biological sciences. Psychology; Genes; Genes. Genome; Genetic engineering; Genetic technics; Glycoproteins - genetics; Humans; Introns; Methods. Procedures. Technologies; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Placenta - metabolism; Plasminogen Activators - antagonists & inhibitors; Plasminogen Inactivators; Pregnancy; Promoter Regions, Genetic; Synthetic digonucleotides and genes. Sequencing
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)76517-X

We have determined the nucleotide sequence of the human plasminogen activator inhibitor-1 (PAI-1) gene and significant stretches of DNA which extend into its 5′-and 3′-flanking DNA regions; a total sequence of 15,867 base pairs (bp) is presented. The sequenced 5′-flanking DNA (1,520 bp) contains the essential eukaryotic cis-type proximal regulatory elements CCAAT and TATAA; the more distal 5′-flanking DNA region, as well as some introns, contain sequence elements which share identities with known eukaryotic enhancer elements. A major finding is the identification of a large region of shared nucleotides (comprising of about 520 bp) between the 5′-flanking DNAs of PAI-1 and tissue-type plasminogen activator genes. The length of the PAI-1 5′-untranslated region was found to be 145 bp as determined by nuclease analysis. The remaining PAI-1 structural gene consists of amino acid coding regions (containing a total of 1,206 bp, coding for the 23 amino acids of the signal peptide and 379 amino acids of the mature PAI-1 protein), 8 intron regions (a total of 8,978 bp), and a long 3′-untranslated region of about 1,800 bp which contains several polyadenylation sites. Two types of repetitive DNA elements are located within the PAI-1 structural gene and flanking DNAs: we have found 12 Alu elements and 5 repeats of a long poly (Pur) element. These Alu-Pur elements may represent a subset of the more abundant Alu family of repetitive sequence elements.