Tet Proteins Connect the O-Linked N-acetylglucosamine Transferase Ogt to Chromatin in Embryonic Stem Cells

O-linked N-acetylglucosamine (O-GIcNAc) transferase (Ogt) activity is essential for embryonic stem cell (ESC) viability and mouse development. Ogt is present both in the cytoplasm and the nucleus of different cell types and catalyzes serine and threonine glycosylation. We have characterized the biochemical features of nuclear Ogt and identified the ten-eleven translocation (TET) proteins Tet1 and Tet2 as stable partners of Ogt in the nucleus of ESCs. We show at a genome-wide level that Ogt preferentially associates with Teti to genes promoters in close proximity of CpG-rich transcription start sites. These regions are characterized by low levels of DNA modification, suggesting a link between Teti and Ogt activities in regulating CpG island nnethylation. Finally, we show that Teti is required for binding of Ogt to chromatin affecting Teti activity. Taken together, our data characterize how O-GIcNAcylation is recruited to chromatin and interacts with the activity of 5-methylcytosine hydroxylases.