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.