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

Pietro Vella, Andrea Scelfo, SriGanesh Jammula, Fulvio Chiacchiera, Kristine Williams, Alessandro Cuomo, Alessandra Roberto, Jesper Christensen, Tiziana Bonaldi, Kristian Helin, Diego Pasini

Research output: Contribution to journalArticle

171 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)645-656
Number of pages12
JournalMolecular Cell
Volume49
Issue number4
DOIs
Publication statusPublished - Feb 21 2013

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Embryonic Stem Cells
Chromatin
Proteins
5-Methylcytosine
CpG Islands
Acetylglucosamine
Transcription Initiation Site
Protein Transport
Threonine
Mixed Function Oxygenases
O-GlcNAc transferase
UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase
Cell Nucleus
Glycosylation
Serine
Methylation
Cell Survival
Cytoplasm
Genome
DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Tet Proteins Connect the O-Linked N-acetylglucosamine Transferase Ogt to Chromatin in Embryonic Stem Cells. / Vella, Pietro; Scelfo, Andrea; Jammula, SriGanesh; Chiacchiera, Fulvio; Williams, Kristine; Cuomo, Alessandro; Roberto, Alessandra; Christensen, Jesper; Bonaldi, Tiziana; Helin, Kristian; Pasini, Diego.

In: Molecular Cell, Vol. 49, No. 4, 21.02.2013, p. 645-656.

Research output: Contribution to journalArticle

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AU - Vella, Pietro

AU - Scelfo, Andrea

AU - Jammula, SriGanesh

AU - Chiacchiera, Fulvio

AU - Williams, Kristine

AU - Cuomo, Alessandro

AU - Roberto, Alessandra

AU - Christensen, Jesper

AU - Bonaldi, Tiziana

AU - Helin, Kristian

AU - Pasini, Diego

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AB - 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.

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