Dna methylation of endothelial cell-enriched genes during in vitro mouse ES cell differentiation and the role of TET protein

Endothelial cell (EC)-enriched genes are regulated by numerous mechanisms, but especially epigenetic mechanisms such as DNA methylation. The current work examines the importance of TET1 and 2 in murine embryonic stem (ES) cells and their relevance to EC-enriched gene expression. The proximal promoters of EC-enriched genes are differentially methylated in expressing versus non-expressing cell types. To examine how this methylation pattern between EC and non-EC is established, we studied ES cells. The DNA methylation pattern was heterogeneous, and partially propagated to daughter cells upon cell division. When in vitro differentiating WT and TET1 and 2 double knockout (DKO) ES cells, the DNA methylation of EC-enriched gene promoters increases at day 4 and day 7 in both cell lines. Despite their hypermenthylation at day 7, EC- enriched gene expression increases in the WT cells but it is blunted in the DKO cells. Suggesting that TET1 and 2 presence in ES cells facilitate the activation of EC-enriched genes later in development.