A nuclear factor that recognizes the metal-responsive elements of human metallothionein IIA gene.
Expression of metallothionein (MT) genes is regulated by heavy metals mainly at the transcriptional level, via cis-acting elements called the metal-responsive elements (MREs). A HeLa cell nuclear factor that recognizes MREs of the human MTIIA (hMTIIA) gene, MREBP, was characterized. Mobility shift assay and DNase I footprinting experiments showed that MREBP binds specifically to several MREs present upstream of the hMTIIA gene. Cadmium and zinc ions inhibited binding of MREBP to a MRE at high concentrations, suggesting a role of MREBP in the negative regulation of the hMTIIA gene. MREBP was partially purified by passing the HeLa nuclear extract over heparin-agarose, Sephacryl S-300, and MRE-Sepharose affinity columns. Blotting experiments showed that a polypeptide with an M(r) of 112,000 is responsible for the MREBP activity.
Koizumi
S
S
Department of Experimental Toxicology, National Institute of Industrial Health, Kawasaki, Japan.
Suzuki
K
K
Otsuka
F
F
D001483:Base Sequence; D002104:Cadmium / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D015342:DNA Probes; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008668:Metallothionein / Q000235:genetics*; D008969:Molecular Sequence Data; D013379:Substrate Specificity; D015032:Zinc / Q000494:pharmacology*
D015342:DNA Probes; D002104:Cadmium; D004247:DNA; D008668:Metallothionein; D015032:Zinc