Structure of mouse metallothionein-I gene and its mRNA

Metallothioneins are small cysteine-rich proteins that bind heavy metals such as zinc, cadmium, copper and mercury1,2. Recent interest in these proteins has focused on the part they play in zinc metabolism and heavy metal detoxification1. Our interest in metallothionein genes stems largely from the observations that these proteins are inducible by both heavy metals and glucocorticoid hormones1,3. To explore the regulation of these genes, we have isolated cDNA and genomic clones corresponding to mouse metallothionein-I (MT-I)4, and have used them to show that both inducers act at the transcriptional level in vivo and in a wide variety of cell lines5–8. We have also shown that the MT-I gene is amplified during selection for cadmium resistance5. To investigate the mechanisms of gene regulation, knowledge of the primary DNA sequence is necessary. Here we present the entire sequence of mouse MT-I gene along with ∼300 bases of 5′ flanking region that presumably includes promoter and regulatory sites. The 5′ mRNA sequence, defined by S1 nuclease mapping, was combined with sequences of the coding and 3′ untranslated regions obtained previously4 to allow a computer prediction of the most stable secondary structure of MT-I mRNA.