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Rapid CommunicationMinireview

Writing and Rewriting the Epigenetic Code of Cancer Cells: From Engineered Proteins to Small Molecules

Pilar Blancafort, Jian Jin and Stephen Frye
Molecular Pharmacology March 2013, 83 (3) 563-576; DOI: https://doi.org/10.1124/mol.112.080697
Pilar Blancafort
School of Anatomy, Physiology, and Human Biology, The University of Western Australia, Crawley, Western Australia, Australia (P.B.); and Division Chemical Biology and Medicinal Chemistry, and Center for Integrative Chemical Biology and Drug Discovery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.J., S.F.)
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Jian Jin
School of Anatomy, Physiology, and Human Biology, The University of Western Australia, Crawley, Western Australia, Australia (P.B.); and Division Chemical Biology and Medicinal Chemistry, and Center for Integrative Chemical Biology and Drug Discovery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.J., S.F.)
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Stephen Frye
School of Anatomy, Physiology, and Human Biology, The University of Western Australia, Crawley, Western Australia, Australia (P.B.); and Division Chemical Biology and Medicinal Chemistry, and Center for Integrative Chemical Biology and Drug Discovery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.J., S.F.)
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Abstract

The epigenomic era has revealed a well-connected network of molecular processes that shape the chromatin landscape. These processes comprise abnormal methylomes, transcriptosomes, genome-wide histone post-transcriptional modifications patterns, histone variants, and noncoding RNAs. The mapping of these processes in large scale by chromatin immunoprecipitation sequencing and other methodologies in both cancer and normal cells reveals novel therapeutic opportunities for anticancer intervention. The goal of this minireview is to summarize pharmacological strategies to modify the epigenetic landscape of cancer cells. These approaches include the use of novel small molecule inhibitors of epigenetic processes specifically deregulated in cancer cells and the design of engineered proteins able to stably reprogram the epigenetic code in cancer cells in a way that is similar to normal cells.

Footnotes

  • dx.doi.org/10.1124/mol.112.080697.

  • Received July 2, 2012.
  • Accepted November 13, 2012.
  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 83 (3)
Molecular Pharmacology
Vol. 83, Issue 3
1 Mar 2013
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Rapid CommunicationMinireview

Writing and Rewriting the Epigenetic Code of Cancer Cells

Pilar Blancafort, Jian Jin and Stephen Frye
Molecular Pharmacology March 1, 2013, 83 (3) 563-576; DOI: https://doi.org/10.1124/mol.112.080697

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Rapid CommunicationMinireview

Writing and Rewriting the Epigenetic Code of Cancer Cells

Pilar Blancafort, Jian Jin and Stephen Frye
Molecular Pharmacology March 1, 2013, 83 (3) 563-576; DOI: https://doi.org/10.1124/mol.112.080697
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  • Article
    • Abstract
    • Introduction
    • The “Language” of Chromatin Modifications
    • Interconnections between DNA Methylation and Histone Methylation
    • Context-Dependence of the Epigenetic Modifications
    • Mechanisms of DNA Demethylation
    • Epigenetic Alterations in Cancer
    • Strategies to Revert the Epigenetic Landscape of Cancer Cells Using Small Molecules and Engineered Proteins
    • Selective Inhibitors of Bromodomains and Methyl-Lysine Readers
    • Selective Inhibitors of Protein Lysine Methyltransferases
    • Artificial Transcription Factors as Locus-specific Epigenetic Modulators
    • ATFs Versus Small Molecule Inhibitors
    • Summary
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
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