Cloned transcription factor MTF-1 activates the mouse metallothionein I promoter
Metallothioneins (MTs) are small cysteine-rich proteins whose structure is conserved from fungi to man. MTs strongly bind heavy metals, notably zinc, copper and cadmium. Upon exposure of cells to heavy metal and other adverse treatments, MT gene transcription is strongly enhanced. Metal induction is mediated by several copies of a 15 bp consensus sequence (metal-responsive element, MRE) present in the promoter region of MT genes. We and others have demonstrated the presence of an MRE-binding factor in HeLa cell nuclear extracts. We found that this factor, termed MTF-1 (MRE-binding transcription factor) is inactivated/reactivated in vitro by zinc withdrawal/addition. Here we report that the amounts of MTF-1-DNA complexes are elevated several-fold in zinc-treated cells, as measured by bandshift assay. We have also cloned the cDNA of mouse MTF-1, a 72.5 kDa protein. MTF-1 contains six zinc fingers and separate transcriptional activation domains with high contents of acidic and proline residues. Ectopic expression of MTF-1 in primate or rodent cells strongly enhances transcription of a reporter gene that is driven by four consensus MREd sites, or by the complete mouse MT-I promoter, even at normal zinc levels.
- URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8467794
Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Cell Line ; Cloning ; Molecular ; DNA-Binding Proteins/genetics ; Gene Expression ; Metallothionein/*genetics ; Mice ; Molecular Sequence Data ; Oligodeoxyribonucleotides/chemistry/metabolism ; *Promoter Regions (Genetics) ; RNA ; Messenger/genetics ; Recombinant Proteins/metabolism ; Transcription Factors/*genetics ; Zinc/physiology ; Zinc Fingers
Universitat Zurich, Institut fur Molekularbiologie II, Switzerland.
Record created on 2006-12-05, modified on 2016-08-08