Polycomb Repressive Complex 2 Methylates Elongin A to Regulate Transcription

Mol Cell. 2017 Dec 7;68(5):872-884.e6. doi: 10.1016/j.molcel.2017.10.025. Epub 2017 Nov 16.


Polycomb repressive complex 2 (PRC2-EZH2) methylates histone H3 at lysine 27 (H3K27) and is required to maintain gene repression during development. Misregulation of PRC2 is linked to a range of neoplastic malignancies, which is believed to involve methylation of H3K27. However, the full spectrum of non-histone substrates of PRC2 that might also contribute to PRC2 function is not known. We characterized the target recognition specificity of the PRC2 active site and used the resultant data to screen for uncharacterized potential targets. The RNA polymerase II (Pol II) transcription elongation factor, Elongin A (EloA), is methylated by PRC2 in vivo. Mutation of the methylated EloA residue decreased repression of a subset of PRC2 target genes as measured by both steady-state and nascent RNA levels and perturbed embryonic stem cell differentiation. We propose that PRC2 modulates transcription of a subset of low expression target genes in part via methylation of EloA.

Keywords: EZH2; Elongin A; Elongin complex; Gene repression; Polycomb repressive complex 2 (PRC2); RNA polymerase II; SPOT assay; protein methylation; transcription.

MeSH terms

  • 3T3-L1 Cells
  • Animals
  • Cell Differentiation*
  • DNA Methylation*
  • Elongin / genetics
  • Elongin / metabolism*
  • Embryonic Stem Cells / metabolism*
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Developmental
  • Histones / genetics
  • Histones / metabolism*
  • Mice
  • Mutation
  • Polycomb Repressive Complex 2 / genetics
  • Polycomb Repressive Complex 2 / metabolism*
  • Transcription, Genetic*
  • Transfection


  • Eloa protein, mouse
  • Elongin
  • Histones
  • Polycomb Repressive Complex 2