Activation of a heterologous promoter in response to dexamethasone and cadmium by metallothionein gene 5'-flanking DNA.
Human metallothionein-IIA (hMT-IIA) gene expression is regulated by heavy metals and glucocorticoids. When the cloned hMT-IIA gene or its 5'-flanking DNA structure fused to herpes simplex virus thymidine kinase (HSV-TK) structural gene sequences were transferred into TK- Rat 2 fibroblasts, both genes were inducible by Cd++ and/or dexamethasone. Placement of the hMT-IIA gene 5'-flanking region, either intact of deleted in its TATA box and cap site, upstream of the HSV-TK gene promoter rendered the latter both glucocorticoid- and heavy metal-inducible. Thus the structure that mediates both Cd++ and glucocorticoid responsiveness is present in the hMT-IIA gene 5'-flanking DNA, does not require its TATA box or cap site, and can activate a heterologous promoter.
D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D002478:Cells, Cultured; D002678:Chimera; D003001:Cloning, Molecular; D003907:Dexamethasone / Q000494:pharmacology*; D005796:Genes / Q000187:drug effects*; D005809:Genes, Regulator / Q000187:drug effects*; D008668:Metallothionein / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D009876:Operon / Q000187:drug effects*; D010957:Plasmids; D051381:Rats; D014158:Transcription, Genetic; D014162:Transfection
D002104:Cadmium; D003907:Dexamethasone; D008668:Metallothionein