Structure and promoter characterization of the human stromelysin-3 gene.
In the present study, we have isolated the human stromelysin-3 (ST3) gene which encodes a matrix metalloproteinase (MMP) expressed in fibroblastic cells of tissues associated with intense remodeling. The gene was found to span 11.5 kilobases (kb) including 8 exons and 7 introns. The genomic organization of ST3 gene exons is well conserved compared to other members of the MMP family, except for the 3 last exons corresponding to the hemopexin-like domain and to a long 3'-untranslated region. The transcription initiation site was located 31 nucleotides downstream of a TATA box. Analysis of 1.4 kb of 5'-flanking DNA sequence in the ST3 gene promoter revealed the presence of putative regulatory elements, but no consensus sequence for AP1-binding site in contrast to other MMP promoters. However, a specific cis-acting retinoic acid responsive element of the DR1 type was identified in the proximal region (-385) of the ST3 gene promoter. Transient transfection experiments demonstrated that a minimal promotor activity could be modulated by various sequences within the 3.4 kb of 5'-flanking region, and that the ST3 promoter was transactivated by retinoic acid receptors in the presence of retinoic acid. These findings indicate that the human ST3 gene promoter is characterized by structural and functional features which differ from those previously described in other MMP promoters, and further supports the possibility that ST3 gene expression is controlled by specific factors during tissue remodeling.
Anglard
P
P
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, C.U. de Strasbourg, France.
Melot
T
T
Guérin
E
E
Thomas
G
G
Basset
P
P
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D002522:Chlorocebus aethiops; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D017931:DNA Primers; D005091:Exons; D005347:Fibroblasts / Q000201:enzymology; D015870:Gene Expression / Q000187:drug effects; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D007438:Introns; D053507:Matrix Metalloproteinase 11; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D016385:TATA Box; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology
D017931:DNA Primers; D011994:Recombinant Proteins; D014212:Tretinoin; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase; D053507:Matrix Metalloproteinase 11; D008666:Metalloendopeptidases