EPIGENETIC EFFECTS OF MINOR GROOVE BINDING LIGANDS

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N.A. Shalginskikh (1), K.I. Kirsanov (1), E.A. Lesovaya (1), G.A. Belitskiy (1), R.A. Katz (2), M.G. Yakubovskaya (1)
1 -Institute of Carcinogenesis N.N. Blokhin Russian Cancer Research Center, Moscow,
2 -Laboratory of molecular structure and function of retroviruses, Fox Chase Cancer Center, Philadelphia

The influence of the DNA minor groove binding ligands on epigenetic silencing in eukaryotic human cells has been demonstrated for the first time. Using HeLa cell population that harbors silent GFP-reporter gene under control of the CMV promoter we demonstrated transcriptional reactivation effect of Hoechst 33342, Hoechst 33258, DAPI, Netropsin, Diminazene and Pentamidine. Total histone acetylation changes were observed under Hoechst 33258 and Hoechst 33342 treatment. In addition Hoechst 33258 was shown to cause a reduction in DNA methylation in the promoter region of the GFP-transgene whereas Hoechst 33342 brought about a decrease in histone H3K4me3 modification.
Keywords: 
epigenetic silencing, DNA methylation, histone modifications, DNA minor groove binding ligands