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Research ArticleSpecial Section on Epigenetic Regulation of Drug Metabolizing Enzymes and Transporters

Potential Role of Epigenetic Mechanisms in the Regulation of Drug Metabolism and Transport

Magnus Ingelman-Sundberg, Xiao-Bo Zhong, Oliver Hankinson, Sudheer Beedanagari, Ai-Ming Yu, Lai Peng and Yoichi Osawa
Drug Metabolism and Disposition October 2013, 41 (10) 1725-1731; DOI: https://doi.org/10.1124/dmd.113.053157
Magnus Ingelman-Sundberg
Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm, Sweden (M.I.-S.); Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut (X.-B.Z., L.P.); Interdepartmental Molecular Toxicology Program and the Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California (O.H., S.B.); Department of Biochemistry and Molecular Medicine, University of California at Davis School of Medicine, Sacramento, California (A.-M.Y.); and Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (Y.O.)
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Xiao-Bo Zhong
Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm, Sweden (M.I.-S.); Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut (X.-B.Z., L.P.); Interdepartmental Molecular Toxicology Program and the Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California (O.H., S.B.); Department of Biochemistry and Molecular Medicine, University of California at Davis School of Medicine, Sacramento, California (A.-M.Y.); and Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (Y.O.)
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Oliver Hankinson
Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm, Sweden (M.I.-S.); Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut (X.-B.Z., L.P.); Interdepartmental Molecular Toxicology Program and the Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California (O.H., S.B.); Department of Biochemistry and Molecular Medicine, University of California at Davis School of Medicine, Sacramento, California (A.-M.Y.); and Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (Y.O.)
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Sudheer Beedanagari
Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm, Sweden (M.I.-S.); Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut (X.-B.Z., L.P.); Interdepartmental Molecular Toxicology Program and the Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California (O.H., S.B.); Department of Biochemistry and Molecular Medicine, University of California at Davis School of Medicine, Sacramento, California (A.-M.Y.); and Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (Y.O.)
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Ai-Ming Yu
Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm, Sweden (M.I.-S.); Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut (X.-B.Z., L.P.); Interdepartmental Molecular Toxicology Program and the Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California (O.H., S.B.); Department of Biochemistry and Molecular Medicine, University of California at Davis School of Medicine, Sacramento, California (A.-M.Y.); and Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (Y.O.)
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Lai Peng
Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm, Sweden (M.I.-S.); Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut (X.-B.Z., L.P.); Interdepartmental Molecular Toxicology Program and the Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California (O.H., S.B.); Department of Biochemistry and Molecular Medicine, University of California at Davis School of Medicine, Sacramento, California (A.-M.Y.); and Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (Y.O.)
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Yoichi Osawa
Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm, Sweden (M.I.-S.); Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut (X.-B.Z., L.P.); Interdepartmental Molecular Toxicology Program and the Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California (O.H., S.B.); Department of Biochemistry and Molecular Medicine, University of California at Davis School of Medicine, Sacramento, California (A.-M.Y.); and Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (Y.O.)
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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.)].

  • dx.doi.org/10.1124/dmd.113.053157.

  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 41 (10)
Drug Metabolism and Disposition
Vol. 41, Issue 10
1 Oct 2013
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Research ArticleSpecial Section on Epigenetic Regulation of Drug Metabolizing Enzymes and Transporters

Epigenetic Mechanisms in Drug Disposition

Magnus Ingelman-Sundberg, Xiao-Bo Zhong, Oliver Hankinson, Sudheer Beedanagari, Ai-Ming Yu, Lai Peng and Yoichi Osawa
Drug Metabolism and Disposition October 1, 2013, 41 (10) 1725-1731; DOI: https://doi.org/10.1124/dmd.113.053157

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Research ArticleSpecial Section on Epigenetic Regulation of Drug Metabolizing Enzymes and Transporters

Epigenetic Mechanisms in Drug Disposition

Magnus Ingelman-Sundberg, Xiao-Bo Zhong, Oliver Hankinson, Sudheer Beedanagari, Ai-Ming Yu, Lai Peng and Yoichi Osawa
Drug Metabolism and Disposition October 1, 2013, 41 (10) 1725-1731; DOI: https://doi.org/10.1124/dmd.113.053157
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  • Article
    • 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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