PMID- 8467794 OWN - NLM STAT- MEDLINE DCOM- 19930513 LR - 20231213 IS - 0261-4189 (Print) IS - 1460-2075 (Electronic) IS - 0261-4189 (Linking) VI - 12 IP - 4 DP - 1993 Apr TI - Cloned transcription factor MTF-1 activates the mouse metallothionein I promoter. PG - 1355-62 AB - 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. FAU - Radtke, F AU - Radtke F AD - Universitat Zurich, Institut fur Molekularbiologie II, Switzerland. FAU - Heuchel, R AU - Heuchel R FAU - Georgiev, O AU - Georgiev O FAU - Hergersberg, M AU - Hergersberg M FAU - Gariglio, M AU - Gariglio M FAU - Dembic, Z AU - Dembic Z FAU - Schaffner, W AU - Schaffner W LA - eng PT - Journal Article PL - England TA - EMBO J JT - The EMBO journal JID - 8208664 RN - 0 (DNA-Binding Proteins) RN - 0 (Oligodeoxyribonucleotides) RN - 0 (RNA, Messenger) RN - 0 (Recombinant Proteins) RN - 0 (Transcription Factors) RN - 9038-94-2 (Metallothionein) RN - J41CSQ7QDS (Zinc) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Cell Line MH - Cloning, Molecular MH - DNA-Binding Proteins/genetics MH - Gene Expression MH - Metallothionein/*genetics MH - Mice MH - Molecular Sequence Data MH - Oligodeoxyribonucleotides/chemistry/metabolism MH - *Promoter Regions, Genetic MH - RNA, Messenger/genetics MH - Recombinant Proteins/metabolism MH - Transcription Factors/*genetics MH - Zinc/physiology MH - Zinc Fingers MH - Transcription Factor MTF-1 PMC - PMC413347 EDAT- 1993/04/01 00:00 MHDA- 1993/04/01 00:01 PMCR- 1994/04/01 CRDT- 1993/04/01 00:00 PHST- 1993/04/01 00:00 [pubmed] PHST- 1993/04/01 00:01 [medline] PHST- 1993/04/01 00:00 [entrez] PHST- 1994/04/01 00:00 [pmc-release] AID - 10.1002/j.1460-2075.1993.tb05780.x [doi] PST - ppublish SO - EMBO J. 1993 Apr;12(4):1355-62. doi: 10.1002/j.1460-2075.1993.tb05780.x.