Transcriptional Regulation of the Metallothionein Genes

Abstract

The classical mammalian metallothioneins (MT-I/II) and the other subfamilies (MT-III/IV) both bind heavy metals by the well-conserved cysteine cluster structure, but their modes of expression differ from each other. MT-I/II is ubiquitously induced by heavy metals, but MT-III/IV is expressed in restricted tissues without obvious dependency on heavy metals. To understand the heavy metal dependent transcriptional activation of the MT-I/II genes, the mechanism of the heavy metal response of a pivotal transcription factor, MTF-1, has been extensively studied. On the other hand, in the case of MT-III, the mechanism of gene suppression has been investigated to clarify the basis of its tissue specific expression. In this review, recent progress in understanding the transcriptional regulation of these MT subfamilies is described.