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 organization and to identify transcription factor binding sites that may be involved in the regulation of human MMP-19 expression, the gene coding for MMP-19 has been cloned and sequenced. The MMP-19 gene spans over 7.6kb and is composed of nine exons and eight introns. Furthermore, a 1.9kb fragment of 5'-flanking DNA was isolated and the transcription start point mapped. Nucleotide sequence analysis of its 5'-flanking region revealed several potential 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 1.9kb MMP-19 promoter fragment and several deletion constructs thereof were able to drive transcription of the luciferase reporter gene in transiently transfected CHO cells. Finally, it has been shown by an electrophoretic mobility shift assay that the AP-1 consensus sequence is able to bind a HeLa nuclear extract derived AP-1 factor.