The novel metallothionein genes of Caenorhabditis elegans. Structural organization and inducible, cell-specific expression

Two genes (mtl-1 and mtl-2) that encode the novel metallothioneins (MTs) of Caenorhabditis elegans (CeMTs) were cloned and characterized. Both genes contain a single intron that interrupts codon 6 and short 3'-untranslated regions. However, their promoter regions are distinctively non-homologous. The mtl-2 promoter contains a TATAA box and a single putative metal regulatory element. These elements are absent in the mtl-1 promoter. Nevertheless, both CeMT1 and CeMT2 mRNAs are induced by cadmium and contain precisely initiated, 5'-untranslated sequences. The inducibility and cell type specificity of metallothionein gene expression were investigated in transgenic C. elegans that carry the lacZ (β-galactosidase) reporter gene under the control of an mtl-1 or mtl-2 promoter sequence. Upon treatment of transgenic C. elegans with cadmium or heat stress, the mtl-2:lacZ fusion gene is abundantly and exclusively expressed in the intestinal cells of larvae and adult animals. Expression is not detected in the absence of metal or heat shock. In contrast, an mtl-1:lacZ construct is constitutively expressed in the pharynx and induced by cadmium and heat shock in the intestinal cells of C. elegans larvae. The metal-inducible expression of the mtl-1:lacZ gene is attenuated in adult transgenic nematodes. Thus, the activity of each mtl promoter is modulated by metals as well as developmental and environmental factors.