First Author | Dalton TP | Year | 1996 |
Journal | J Biol Chem | Volume | 271 |
Issue | 42 | Pages | 26233-41 |
PubMed ID | 8824273 | Mgi Jnum | J:36042 |
Mgi Id | MGI:83493 | Doi | 10.1074/jbc.271.42.26233 |
Citation | Dalton TP, et al. (1996) Oxidative stress activates metal-responsive transcription factor-1 binding activity. Occupancy in vivo of metal response elements in the metallothionein-I gene promoter. J Biol Chem 271(42):26233-41 |
abstractText | Oxidative stress (tert-butylhydroquinone) rapidly induced metallothionein-I gene expression in mouse Hepa cells, and this effect was mediated predominantly through metal response promoter elements in transient transfection assays. In vivo genomic footprinting of the mouse metallothionein-I promoter after treatment of Hepa cells with hydrogen peroxide, tert-butylhydroquinone, or zinc suggested a rapid increase in occupancy of the metal response elements. More subtle changes also occurred in the constitutive genomic footprint at the composite major late transcription factor/antioxidant response element. This element may, in part, mediate induction by hydrogen peroxide. Electrophoretic mobility shift assays demonstrated a rapid (30 min) increase in the DNA binding activity of metal-responsive transcription factor-1 in Hepa cells treated with any of these inducers. In control cells, upstream stimulatory factor binding with the major late transcription factor site, and a nuclear protein complex distinct from AP-1, but specific for the antioxidant response element, were detected. The amounts of these complexes were not altered after these treatments. These studies indicate that metal-responsive transcription factor-1 plays a role in activating mouse metallothionein-I gene transcription in response to reactive oxygen species. |