Some organotin compounds enhance histone acetyltransferase activity.
Eukaryotic DNA is packaged into chromatin, whose basic subunit is the nucleosome, which consists of DNA and a core histone octamer. Histone acetylation is important for the regulation of gene expression and is catalyzed by histone acetyltransferase (HAT). We observed the effects of suspected endocrine-disrupting chemicals (EDCs) on HAT activity. We showed that some organotin compounds--tributyltin (TBT) and triphenyltin (TPT)--enhanced HAT activity of core histones in a dose-dependent way and other EDCs did not affect HAT activity. Organotin compounds have various influences on physical function including the hormone and immune systems, embryogenesis, and development. Dibutyltin and diphenyltin, metabolites of TBT and TPT, respectively, also promoted HAT activity, but monobutyltin, monophenyltin, and inorganic tin had no effect. Further, TBT and TPT enhanced HAT activity when nucleosomal histones were used as substrates. These data indicate that the organotin compounds have unique effects on HATs independent of their EDC activities and suggest that the varied toxicities of the organotin compounds may be caused by aberrant gene expression following altered histone acetylation.
Osada
Shigehiro
S
Laboratory of Environmental Biochemistry, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-Oka, Suita, Osaka 565-0871, Japan. osada@phs.osaka-u.ac.jp
Nishikawa
Jun-ichi
J
Nakanishi
Tsuyoshi
T
Tanaka
Keiichi
K
Nishihara
Tsutomu
T
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism*; D008099:Liver / Q000166:cytology; D009707:Nucleosomes / Q000201:enzymology* / Q000378:metabolism; D009947:Organotin Compounds / Q000633:toxicity*; D051381:Rats
D006657:Histones; D009707:Nucleosomes; D009947:Organotin Compounds; D000123:Acetyltransferases; D051548:Histone Acetyltransferases