A zinc-responsive factor interacts with a metal-regulated enhancer element (MRE) of the mouse metallothionein-I gene

EMBO J. 1988 Dec 1;7(12):3763-70.

Abstract

Heavy metal ions are effective inducers of metallothionein gene transcription. The metal response is dependent on short DNA motifs, so-called MREs (metal responsive elements) that occur in multiple copies in the promoter region of these genes. We have analysed an MRE of the mouse metallothionein-I gene (MREd) and we demonstrate that this can function over long distances as a bona fide metal ion-inducible enhancer. The transcription factor Sp1 and a zinc-inducible factor, designated MTF-1, bind to the MREd enhancer in vitro. The combined use of MREd mutants in a transient assay in HeLa cells and a competition band shift assay show that the zinc-inducible formation of the MTF-1/DNA complex in vitro correlates with zinc-inducible transcription in vivo. A chemical methylation interference assay revealed remarkably similar but non-identical guanine interference patterns for the MTF-1 and Sp1 complexes, which may mean that MTF-1 is related to the Sp1 factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • DNA Mutational Analysis
  • DNA, Recombinant
  • DNA-Binding Proteins / physiology*
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation*
  • HeLa Cells
  • In Vitro Techniques
  • Macromolecular Substances
  • Metallothionein / genetics*
  • Mice
  • Transcription Factors / physiology*
  • Transcription, Genetic
  • Zinc / pharmacology*

Substances

  • DNA, Recombinant
  • DNA-Binding Proteins
  • Macromolecular Substances
  • Transcription Factors
  • Metallothionein
  • Zinc