Polycomb repressive complex 2 is necessary for the normal site-specific O-GlcNAc distribution in mouse embryonic stem cells

Proc Natl Acad Sci U S A. 2011 Jun 7;108(23):9490-5. doi: 10.1073/pnas.1019289108. Epub 2011 May 23.


The monosaccharide addition of an N-acetylglucosamine to serine and threonine residues of nuclear and cytosolic proteins (O-GlcNAc) is a posttranslational modification emerging as a general regulator of many cellular processes, including signal transduction, cell division, and transcription. The sole mouse O-GlcNAc transferase (OGT) is essential for embryonic development. To understand the role of OGT in mouse development better, we mapped sites of O-GlcNAcylation of nuclear proteins in mouse embryonic stem cells (ESCs). Here, we unambiguously identify over 60 nuclear proteins as O-GlcNAcylated, several of which are crucial for mouse ESC cell maintenance. Furthermore, we extend the connection between OGT and Polycomb group genes from flies to mammals, showing Polycomb repressive complex 2 is necessary to maintain normal levels of OGT and for the correct cellular distribution of O-GlcNAc. Together, these results provide insight into how OGT may regulate transcription in early development, possibly by modifying proteins important to maintain the ESC transcriptional repertoire.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylglucosamine / metabolism*
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Blotting, Western
  • Cells, Cultured
  • Chromatography, Liquid
  • Embryonic Stem Cells / metabolism*
  • Glycosylation
  • Mass Spectrometry
  • Mice
  • Molecular Sequence Data
  • Mutation
  • N-Acetylglucosaminyltransferases / genetics
  • N-Acetylglucosaminyltransferases / metabolism*
  • Nuclear Proteins / metabolism
  • Peptides / metabolism
  • Polycomb-Group Proteins
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*


  • Nuclear Proteins
  • Peptides
  • Polycomb-Group Proteins
  • Repressor Proteins
  • N-Acetylglucosaminyltransferases
  • O-GlcNAc transferase
  • Acetylglucosamine