A Krox Binding Site Regulates Protease Nexin-1 Promoter Activity in Embryonic Heart, Cartilage and Parts of the Nervous System

The rat protease nexin-1 (PN-1) promoter contains a GCGGGGGCG binding site for the transcription factors Krox-24, Krox-20 and NGFI-C. Mutations of this site abolished binding of Krox-24 in vitro. The wildtype protease nexin-1 promoter expressed beta-galactosidase similarity to the expression of protease nexin-1 mRNA. When the function of this Krox site was tested in vivo using transgenic F0 embryos, mutation had two opposite effects. beta-Galactosidase expression increased in cartilage and heart at both stages E11.5 and E13.5, but was abolished in nerves of the central and peripheral nervous system at stage E13.5. These results suggest that Krox factors are among the important transcription factors regulating protease nexin-1 expression and thereby intracellular proteolytic activity in embryonic heart, cartilage and parts of the nervous system.