Role of cytidine deaminases in epigenetic reprogramming and demethylation of DNA

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All genes in the genome of humans and other mammals are now known. However we have little knowledge about which signals are needed for genes to switch on and off during development of a new organism from embryo to adult. An important signal are instructions that are attached to DNA in the form of small chemical molecules (methyl-groups). These are usually attached to genes when they need to be off. When genes need to be switched on, the methyl-groups need to be removed from the DNA; this is particularly important at the beginning of development in the very early embryo. When this switching is defective it can give rise to diseases of embryonic development and many cancers have aberrant ?epigenetic? switching of this type. Our current work has identified a mechanism for the removal of the methyl-signals from DNA, and in work under this grant we will gain a better understanding how this mechanism works in embryos, in order to harness its activities for stem cell ?regenerative? medicine and cures for cancer.