Lineage-specific epigenetic regulation by DNA oxygenase TET1 in the pre-streak mouse embryo

In mammals, early embryonic cells can generate the entire body during development, by changing dynamically how information in their genetic material, or DNA, is interpreted by proteins that bind to turn on or off the messages. Chemical marks added to DNA, called methylation, also affect how messages are read in the cell. Here, we examine the mouse embryo soon after implantation in the uterus, to see how DNA methylation marks are patterned to affect development. Specifically, we ask how a protein that removes these marks, TET1, manages the patterns to control which regions are available to bind other important proteins. We recently observed that TET1 is present in both primitive cell types in the embryo that produce either the fetus or the placenta, and has different functions in each. We will use a mouse which contains markers in its DNA to show whether TET1 is present or absent, to study its cell-type specific functions. Because embryos that lack TET1 develop defects in the early brain that look like congenital defects common in human pregnancies, we will use our mouse as a model to understand how different parts of the embryo contribute to the disorder. Finally, we will use these insights in the mouse to study cells in laboratory dishes, to understand how they are controlled by TET1 after committing to the placental lineage. These studies will provide important new information of how abnormal DNA methylation marks in early development can result in disease later in life.