Regulation in vitro of metallothionein gene binding factors.

Mouse nuclear factors that bind to an upstream metal regulatory element of the mouse metallothionein-I gene have been identified by DNA footprinting and oligonucleotide band shift assays. The formation of complexes at this site can be activated 20- to 40-fold by the vitro addition of ionic cadmium. The activation reaction is rapid, reversible by a metal chelator, and may involve multiple proteins. These results suggest that the initial step in cadmium detoxification is an interaction between the metal and nuclear DNA-binding factors leading to an increase in metallothionein gene transcription. The ability to observe metal activation in vitro makes this a powerful system to study the biochemistry of eukaryotic gene regulation.