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High-content fluorescence-based screening for epigenetic-modulators

  1. Author:
    Martinez, E. D.
    Dull, A. B.
    Beutler, J. A.
    Hager, G. L.

  2. Author Address

    NCI, Lab Receptor Biol & Gene Express, Hormone Act & Oncogenesis Sect, NIH, Bethesda, MD 20892 USA. SAIC Frederic INc, Basic Res Program, Mol Targets Dev Program, NCI,NIH, Frederick, MD 21701 USA.;Martinez, ED, NCI, Lab Receptor Biol & Gene Express, Hormone Act & Oncogenesis Sect, NIH, Bethesda, MD 20892 USA.
    1. Year: 2006
  2. Book Title: Measuring Biological Responses with Automated Microscopy
  3. Series Title: Methods in Enzymology
  4. Elsevier Academic Press Inc
  5. San Diego
    1. 414
    2. Pages: 21-36
  7. Type of Work: Review
  8. ISBN: 0076-6879
  1. Abstract:

    Epigenetic processes have gained a great amount of attention in recent years, particularly due to the influence they exert on gene transcription. Several human diseases, including cancer, have been linked to aberrant epigenetic pathways. Consequently, the cellular enzymes that mediate epigenetic events, including histone deacetylases and DNA methyltransferases, have become prime molecular targets for therapeutic intervention. The effective and specific chemical inhibition of these activities is a top priority in cancer research and appears to have therapeutic potential. This chapter describes the development of mammalian cell-based fluorescent assays to screen for epigenetic modulators using an innovative combination of approaches. Detailed protocols for the use of the assays in drug screens, as well as for the initial characterization of hits, are provided. Furthermore, options for evaluating the mechanism of action of these compounds are presented and principles to govern the choice of hit compounds for the development of leads are discussed.

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External Sources

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  2. DOI: 10.1016/s0076-6879(06)14002-1
  3. View record in Web of Science®
  4. WOS: 000243221500002

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