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Several decades after the first observation of DNA modifications in mammals, we still do not know why some DNA bases are modified and whether it really matters to begin with. Although there are only three DNA methyltransferases (DNMTs) and three DNA oxygenases (TETs), an infinite number of DNA modification patterns can be observed throughout development and disease. Over the past decades, several functional links with other epigenetic pathways and cellular metabolism have been described. In this talk, I will focus on the surprising and opposing roles of TET, UHRF1 and DPPA3 in the regulation of DNA modifications and pluripotency. I will present data on the pivotal role of ubiquitination in regulating DNA modifications, as well as new regulatory mechanisms.
