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. 1994 Feb 15;91(4):1219–1223. doi: 10.1073/pnas.91.4.1219

Regulation of metallothionein genes by heavy metals appears to be mediated by a zinc-sensitive inhibitor that interacts with a constitutively active transcription factor, MTF-1.

R D Palmiter 1
PMCID: PMC43128  PMID: 8108390

Abstract

A construct, MRE-beta Geo, with five metal response elements fused to a selectable reporter gene was transfected into BHK cells and a stable clone that could be induced up to 100-fold by zinc, cadmium, bismuth, silver, cobalt, copper, mercury, or nickle was isolated. Some, and perhaps all, of these metals induce MRE-beta Geo by displacing zinc. Transfection of these cells with a construct encoding the transcriptional activator MTF-1 resulted in constitutive expression of MRE-beta Geo, whereas expression of an antisense MTF-1 construct in these cells prevented induction by all of the metals. A variant cell line with high constitutive expression in the absence of added metals was isolated; normal regulation was restored by cell fusion. These results suggest that regulation of metallothionein genes by metals is mediated by MTF-1 interacting with metal response elements and that zinc functions to release MTF-1 from an inhibitor.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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