Regulation of the rat metallothionein-I gene by sodium butyrate.
Sodium butyrate selectively induces accumulation of metallothionein-I (MT-I) RNA in H4IIE rat hepatoma cells. The induction is rapid; significant elevation in cytoplasmic MT-I RNA can be observed within three hours after exposure to 5 mM butyrate. Maximal levels of MT-I RNA are obtained after eight hours. Butyrate stimulates MT RNA accumulation in the absence of de novo protein synthesis, indicating that MT induction by butyrate is not a distal step in a cascade of gene activation events. Butyrate blocks the induction of tyrosine amino transferase by dexamethasone. In contrast, butyrate and dexamethasone induced MT RNA elevations are additive. Butyrate induced MT-I RNA transcripts initiate at the correct start site. Measurements of the transcriptional activity of the MT-I gene indicate that butyrate stimulates MT-I transcription. The rapid, direct nature of the induction of MT-I by butyrate, combined with the extensive characterization of the metallothionein gene, provide an excellent system in which to study the effects of butyrate on a small, well-defined, responsive region of chromatin.
Birren
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BW
Herschman
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HR
D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D003593:Cytoplasm / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D005796:Genes / Q000187:drug effects*; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008668:Metallothionein / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D014444:Tyrosine Transaminase / Q000096:biosynthesis
D002087:Butyrates; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D020148:Butyric Acid; D003907:Dexamethasone; D008668:Metallothionein; D014444:Tyrosine Transaminase