Abstract 4915: Global epigenomic modification platform

DNA methylation is an epigenetic mechanism that governs gene silencing and this silencing could be reversed. Pre-deposited global DNA methylation during differentiation is associated with cell fate determination and abnormal DNA methylation could lead to tumorigenesis. A global DNA methylation manipulation system is thus hypothesized to control the differentiation and tumorigenesis more efficiently. Two platforms were established to loss or gain of DNA methylation genome-wide. For the loss of DNA methylation, an in vivo methylation monitoring system was employed to screen 169 procainamide derivatives and identified three distinct classes of these compounds based on their cytotoxicity and demethylation potency. For the gain of DNA methylation, a global DNA methylation subtraction method was developed to identify and methylate target loci genome-wide. After targeted methylation globally, the drug resistance of cancer cells was reverted to become drug sensitive. The same method was used to identify and methylate the hypomethylated loci within somatic stem cells when compared with the differentiated neuronal cells. The targeted methylation accelerated the differentiation of the somatic stem cell to become neuron-like. With both platforms, we wish to evaluate if global DNA methylation changes is sufficient to steer the cell fate. (Supported in part by NSC 97-2320-B-194-003-MY3, NSC 98-3112-B-194-001 and NSC 97-2627-B-006-003) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4915.