Molecular Biology of Metallothionein Gene Expression

During the seven years since the 1st International Meeting on Metallothionein, the metallothionein (MT) genes have been isolated from a number of organisms and the molecular analysis of their expression has begun. MT genes are expressed in most tissues of most organisms studied. However, in some cells they are transcriptionally inactive, apparently as a consequence of DNA methylation. In those cells that can express MT genes, they are transcriptionally regulated by metals, glucocorticoid, and/or several polypeptide hormones. Some of the DNA sequences that allow response to these stimuli have been identified in the 5′ flanking region of the MT genes. Cells with extra copies of the MT genes can be selected by exposure to toxic concentrations of cadmium. Because the MT promoter can direct a high level of metal-inducible expression in a variety of cell types, it has been linked to many different structural genes and these fusion genes have been introduced into tissue culture cells and into the germline of animals. The analysis of MT gene regulation and its applications to genetic engineering have introduced this fascinating system to a much wider scientific community. In this review, I outline the highlights of MT gene regulation. A short minireview covering some aspects of MT gene regulation has appeared (1) and an extensive review will be available soon (2).