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Publication : Oxidative stress activates metal-responsive transcription factor-1 binding activity. Occupancy in vivo of metal response elements in the metallothionein-I gene promoter.

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.
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