TY - JOUR
T1 - High-Content Fluorescence-Based Screening for Epigenetic Modulators
AU - Martinez, Elisabeth D.
AU - Dull, Angie B.
AU - Beutler, John A.
AU - Hager, Gordon L.
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33750843009&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750843009&partnerID=8YFLogxK
U2 - 10.1016/S0076-6879(06)14002-1
DO - 10.1016/S0076-6879(06)14002-1
M3 - Article
C2 - 17110184
AN - SCOPUS:33750843009
SN - 0076-6879
VL - 414
SP - 21
EP - 36
JO - Methods in Enzymology
JF - Methods in Enzymology
ER -