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

SummaryO-linked N-acetylglucosamine (O-GlcNAc) 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 Tet1 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 Tet1 and Ogt activities in regulating CpG island methylation. Finally, we show that Tet1 is required for binding of Ogt to chromatin affecting Tet1 activity. Taken together, our data characterize how O-GlcNAcylation is recruited to chromatin and interacts with the activity of 5-methylcytosine hydroxylases.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (107 K)Download as PowerPoint slideHighlights► Ogt forms a complex with Tet1 and Tet2 in the nucleus of embryonic stem cells ► Ogt preferentially associates with promoter regions in proximity of TSS ► Ogt shows >90% of colocalization with Tet1 at methylation-free CpG-rich elements ► Tet1 is required for global Ogt chromatin recruitment regulating its activity