Induction of reporter gene expression by inhibitors of histone deacetylase.
The relationship between histone acetylation and induction of gene expression was studied in Ros 17/2.8 rat osteosarcoma cells transfected with the pCH110 plasmid. This plasmid is commonly used in cotransfections as a measure of transfection efficiency. Cells were incubated for 48 hours with sodium butyrate, phenylbutyrate, 3-bromopropionate or trichostatin A. There was an approximate relationship between the extent of beta-galactosidase induction and the degree of histone hyperacetylation. Trichostatin A was the most effective agent followed by sodium butyrate and then phenylbutyrate. The toxicity of 3-bromopropionate made it difficult to compare its action with the other agents. Phenylbutyrate was less effective than sodium butyrate in causing induction of gene expression and histone hyperacetylation but this action may be a factor in the growth-inhibitory and differentiating activity of phenylbutyrate which has also been attributed to glutamine depletion.
Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School, Newark 07103, USA. lea@umdnj.edu
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Randolph
D000818:Animals; D001859:Bone Neoplasms; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017930:Genes, Reporter; D006655:Histone Deacetylases / Q000096:biosynthesis*; D006877:Hydroxamic Acids / Q000494:pharmacology; D012516:Osteosarcoma; D010654:Phenylbutyrates / Q000494:pharmacology; D010957:Plasmids; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000096:biosynthesis*
D002087:Butyrates; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D010654:Phenylbutyrates; D011422:Propionates; D011994:Recombinant Proteins; D020148:Butyric Acid; C012589:trichostatin A; D001616:beta-Galactosidase; D006655:Histone Deacetylases; C035776:3-bromopropionic acid