Abstract
This is a report of a symposium on the potential role of epigenetic mechanisms in the control of drug disposition sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 2013 meeting in Boston, MA, April 21, 2013. Epigenetics is a rapidly evolving area, and recent studies have revealed that expression of drug-metabolizing enzymes and transporters is regulated by epigenetic factors, including histone modification, DNA methylation, and noncoding RNAs. The symposium speakers provided an overview of genetic and epigenetic mechanisms underlying variable drug metabolism and drug response, as well as the implications for personalized medicine. Considerable insight into the epigenetic mechanisms in differential regulation of the dioxin-inducible drug and carcinogen-metabolizing enzymes CYP1A1 and 1B1 was provided. The role of noncoding microRNAs in the control of drug metabolism and disposition through targeting of cytochrome P450 (P450) enzymes and ATP-binding cassette membrane transporters was discussed. In addition, potential effects of xenobiotics on chromatin interactions and epigenomics, as well as the possible role of long noncoding RNAs in regulation of P450s during liver maturation were presented.
Footnotes
- Received May 30, 2013.
- Accepted August 5, 2013.
This work was supported by The Swedish Research Council (M.I.-S.); the National Institutes of Health National Institute of Environmental Health Sciences [Grants R01-ES015384 (to O.H.) and R01-ES019487 (to X.-B.Z.,)]; National Institute on Drug Abuse [Grant R01DA021172 (to A.-M.Y.)]; and National Institute of General Medical Sciences [Grants R01-GM087376 (to X.-B.Z.) and R01GM077430 (to Y.O.)].
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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- Abstract
- Introduction
- Overview of Genetic and Epigenetic Mechanisms Underlying Variable Drug Metabolism and Drug Response (M.I.-S.)
- Role of Epigenetic Mechanisms in Differential Regulation of the Dioxin-Inducible Human CYP1A1 and CYP1B1 Genes (O.H. and S.B.)
- Chromatin Interactions, Epigenomics, and Transcriptional Outcomes in Response to Xenobiotics (X.-B.Z.)
- Noncoding MicroRNAs in the Control of Drug Metabolism and Transport (A.-M.Y)
- Long Noncoding RNAs and Transcriptional and Post-Transcriptional Regulation of Cytochromes P450 in Mouse Liver during Maturation (L.P.)
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