Tet proteins connect the O-linked N-acetylglucosamine transferase Ogt to chromatin in embryonic stem cells.
O-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.
Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy.
Pietro
P
Vella
Andrea
A
Scelfo
Sriganesh
S
Jammula
Fulvio
F
Chiacchiera
Kristine
K
Williams
Alessandro
A
Cuomo
Alessandra
A
Roberto
Jesper
J
Christensen
Tiziana
T
Bonaldi
Kristian
K
Helin
Diego
D
Pasini
D000818:Animals; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002843:Chromatin; D018899:CpG Islands; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D049308:Dioxygenases; D053595:Embryonic Stem Cells / Q000201:enzymology* / Q000378:metabolism; D005786:Gene Expression Regulation; D047468:Immunoprecipitation; D053858:Metabolic Networks and Pathways / Q000235:genetics; D051379:Mice; D017351:N-Acetylglucosaminyltransferases / Q000302:isolation & purification / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000302:isolation & purification / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D024363:Transcription Initiation Site
D002843:Chromatin; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C540839:TET1 protein, mouse; D049308:Dioxygenases; C551914:Tet2 protein, mouse; D017351:N-Acetylglucosaminyltransferases; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase