The homologue of the rat pancreatic elastase I gene was found in the human genome, but its transcription was completely suppressed in the adult human pancreas as we reported previously. In this study, we characterized the complete structure of the eight putative exons of the silent gene for human elastase I. A genotype analysis of the exon 1 DNA sequence revealed that at least two allelic elastase I genes are present in human genomes. A primate-specific repetitive DNA element (MER1) was identified in the 3'-flanking region of the human elastase I gene. The primary structure of human preproelastase I, deduced from the sequences of the eight exons, showed an 89% identity with that of porcine or rat pancreatic preproelastase I. The amino acid residues of the serine protease catalytic triad and the eight cysteine residues conserved in the elastase family were present at positions equivalent to those observed in porcine and rat elastase I, suggesting that the gene product may function as an elastolytic enzyme if this gene is expressed in any tissue.
Recombinant adipogenesis inhibitory factor (AGIF) was purified to homogeneity from the conditioned medium of COS‐1 cells transfected with human AGIF cDNA. The amino‐terminal sequence analysis of the mature AGIF revealed that AGIF was produced as a precursor consisting of 199 amino acids and processed into a mature form of 178 amino acids by a cleavage between Ala(−1) and Pro(+1). The purified AGIF inhibited the process of adipogenesis in mouse 3T3‐L1 preadipocytes, indicating that AGIF directly acts on the cells. AGIF acted as an adipogenic antagonist not only on the extramedullary cell line 3T3‐L1 but also on the mouse bone marrow stroma‐derived cell line H‐I/A, suggesting that this cytokine may regulate adipogenesis in bone marrow.
Computer analyses of the 3'-flanking DNA sequence of the human elastase I gene revealed a significant degree of similarity with seven human gene sequences in the GenBank and EMBL databases. Genomic Southern analysis indicates that the shared nucleotide sequences are a primate-specific family of short interspersed elements. These elements are members of MER1 sequences (medium reiteration frequency sequences). The consensus sequence of MER1 repeats spans 543 nucleotides and contains several inverted repeats. Since the copy number of MER1 elements seems to be much smaller than that of Alu and L1 repeats, MER1 elements may provide useful landmarks marks for human genome mapping.
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