Structure of the human MMP-19 gene

The recently identified MMP-19 belongs to the multi-protein family of zinc- binding matrix metalloproteinases (MMP). In order to analyze its genomic or ganization and to identify transcription factor binding sites that may be i nvolved in the regulation of human MMP-19 expression, the gene coding for M MP-19 has been cloned and sequenced. The MMP-19 gene spans over 7.6 kb and is composed of nine exons and eight introns. Furthermore, a 1.9 kb fragment of 5'-flanking DNA was isolated and the transcription start point mapped. Nucleotide sequence analysis of its 5'-flanking region revealed several pot ential transcription factor binding sites typical of MMP promoters. Thus, a TATA-box, a consensus AP-1 binding element, and a putative PEA3 site were identified. The 1.9 kb MMP-19 promoter fragment and several deletion constr ucts thereof were able to drive transcription of the luciferase reporter ge ne in transiently transfected CHO cells. Finally, it has been shown by an e lectrophoretic mobility shift assay that the AP-1 consensus sequence is abl e to bind a HeLa nuclear extract derived AP-1 factor. (C) 2000 Elsevier Sci ence B.V. All rights reserved.