Spatial Interplay between Polycomb and Trithorax Complexes Controls Transcriptional Activity in T Lymphocytes

Mol Cell Biol. 2015 Nov;35(22):3841-53. doi: 10.1128/MCB.00677-15. Epub 2015 Aug 31.


Trithorax group (TrxG) and Polycomb group (PcG) proteins are two mutually antagonistic chromatin modifying complexes, however, how they together mediate transcriptional counter-regulation remains unknown. Genome-wide analysis revealed that binding of Ezh2 and menin, central members of the PcG and TrxG complexes, respectively, were reciprocally correlated. Moreover, we identified a developmental change in the positioning of Ezh2 and menin in differentiated T lymphocytes compared to embryonic stem cells. Ezh2-binding upstream and menin-binding downstream of the transcription start site was frequently found at genes with higher transcriptional levels, and Ezh2-binding downstream and menin-binding upstream was found at genes with lower expression in T lymphocytes. Interestingly, of the Ezh2 and menin cooccupied genes, those exhibiting occupancy at the same position displayed greatly enhanced sensitivity to loss of Ezh2. Finally, we also found that different combinations of Ezh2 and menin occupancy were associated with expression of specific functional gene groups important for T cell development. Therefore, spatial cooperative gene regulation by the PcG and TrxG complexes may represent a novel mechanism regulating the transcriptional identity of differentiated cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism
  • Cell Line
  • Cells, Cultured
  • Embryonic Stem Cells / metabolism
  • Enhancer of Zeste Homolog 2 Protein
  • Genome
  • Mice, Inbred C57BL
  • Polycomb Repressive Complex 2 / metabolism*
  • Protein Binding
  • Proto-Oncogene Proteins / metabolism*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism*
  • Transcription Initiation Site
  • Transcriptional Activation*


  • Men1 protein, mouse
  • Proto-Oncogene Proteins
  • Enhancer of Zeste Homolog 2 Protein
  • Ezh2 protein, mouse
  • Polycomb Repressive Complex 2