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Some organotin compounds enhance histone acetyltransferase activity
Shigehiro Osada1, Jun-ichi Nishikawa, Tsuyoshi Nakanishi
1Laboratory 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
Toxicology Letters
|December 18, 2004
Summary
Certain organotin compounds, like tributyltin (TBT) and triphenyltin (TPT), enhance histone acetyltransferase (HAT) activity. This suggests organotins may cause toxicity by altering gene expression through histone acetylation.
Area of Science:
- Biochemistry
- Molecular Biology
- Toxicology
Background:
- Eukaryotic DNA is packaged into chromatin, with nucleosomes as basic subunits.
- Histone acetylation, regulated by histone acetyltransferase (HAT), is crucial for gene expression.
- Endocrine-disrupting chemicals (EDCs) can interfere with biological processes.
Purpose of the Study:
- To investigate the effects of suspected endocrine-disrupting chemicals (EDCs) on histone acetyltransferase (HAT) activity.
- To determine if organotin compounds, known EDCs, impact HAT activity and gene regulation.
Main Methods:
- Assayed HAT activity using core histones and nucleosomal histones as substrates.
- Tested various organotin compounds, including tributyltin (TBT), triphenyltin (TPT), and their metabolites.
- Observed dose-dependent effects of organotins on HAT activity.
Main Results:
- Tributyltin (TBT) and triphenyltin (TPT) dose-dependently enhanced HAT activity of core histones.
- Metabolites dibutyltin and diphenyltin also promoted HAT activity.
- Monobutyltin, monophenyltin, and inorganic tin showed no effect on HAT activity.
Conclusions:
- Organotin compounds uniquely affect HAT activity, independent of their endocrine-disrupting properties.
- Altered histone acetylation by organotins may lead to aberrant gene expression and varied toxicities.
- These findings highlight a novel mechanism for organotin toxicity.