The regulation and function of metallothioneins are being analyzed by molecular genetic and biochemical approaches in both mammalian cells and yeast. A mouse nuclear protein that interacts with the heavy metal control sequences of the mouse metallothionein-I gene has been detected and is regulated by cadmium in vitro. The structural basis for differential metal binding of human metallothionein-I isoform genes has been investigated by gene shuffling and transfer experiments. Regulation of these genes during development and by oncogenes is also being studied. In yeast, trans-acting mutants that alter metallothionein gene regulation have been isolated. A substantial number of mutants have been engineered into the yeast metallothionein coding sequence and are proving useful in determining the role of individual amino acids in its structure and function.
