A zinc-responsive factor interacts with a metal-regulated enhancer element (MRE) of the mouse metallothionein-I gene.
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.
Westin
G
G
Institut für Molekularbiologie II der Universität Zürich, Switzerland.
Schaffner
W
W
D000818:Animals; D001665:Binding Sites; D004252:DNA Mutational Analysis; D004274:DNA, Recombinant; D004268:DNA-Binding Proteins / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006367:HeLa Cells; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008668:Metallothionein / Q000235:genetics*; D051379:Mice; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D015032:Zinc / Q000494:pharmacology*
D004274:DNA, Recombinant; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D014157:Transcription Factors; D008668:Metallothionein; D015032:Zinc