Avian metallothioneins: structure, regulation and evolution

This article reviews studies of the molecular biology of the avian metallothionein (MT) genes. Analysis of cloned genes and/or cDNAs from chicken, turkey, pheasant and quail suggests that each of these species possesses a very simple MT gene family. The MT from these birds is a cysteine-rich protein of 63 amino acids that shares extensive structural homology with the mammalian MTs, and, remarkably, the deduced amino acid sequence of the major metallothionein is identical in each of these birds. The chicken MT gene is inducible by dietary or injected metal ions [i.e., zinc (Zn) and copper (Cu)], bacterial lipopolysaccharide and oxidative stress. Furthermore, it is expressed during liver development. The turkey and chicken MT genes are identical in gross structure to other functional MT genes. They consist of three exons separated by two intervening sequences. Comparisons of the nucleotide sequences of the turkey and chicken MT genes revealed regions of exceptionally high sequence conservation, suggesting important functions such as splicing, polyadenylation and transcriptional activation. Structure-function studies of the chicken MT promoter using transient transfection assays and transgenic mice have revealed cis-acting promoter sequences involved in the induction of chicken MT gene expression by metals ions. A metal-responsive enhancer was located in the proximal 107-bp of the chicken MT promoter in a region highly conserved in both the turkey and chicken MT genes. Function of this enhancer element apparently requires cooperation of transcription factors interacting with an Sp 1 binding site and a single palindromic metal-responsive element. In this regard, the structure of the proximal region of the chicken and turkey MT promoters is unique. Our current studies suggest that this enhancer regulates gene expression in a position-independent manner in transgenic mice.