De rol van TET1-gemedieerde DNA-demethylatie in de neurologische ontwikkeling bij muis en mens

In mammalian cells, the genetic information encoded in DNA is coated by chemical marks called methylation, often to turn off gene messages. Widespread removal of these marks is critical in embryonic and germ cells to reset the developmental life cycle clock. Similarly, experimental methods to revert adult cells to embryonic-like cells, called induced pluripotent stem cells (iPSCs), involve global loss of DNA methylation in the final stages, but how that affects gene expression are not understood. Here, we study a class of proteins called TET that removes DNA methylation. Using mouse tissues, we examine how cells lose DNA methylation in the final steps to becoming iPSCs. In these cells, we use new sequencing technologies to understand the process by which DNA regions open and tightly associated proteins change in status to reflect gene activation or silencing. In doing so, we aim to learn new ways genes are controlled whenever there is global loss of DNA methylation. We will find out the extent by which TET proteins actively remove DNA methylation and affect gene expression in the final steps of iPSC formation. Finally, we ask if turning on TET1 fully in human PSCs will improve their quality and safety for research and clinical applications.