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Polycomb Repressive Complex 2 Methylates Elongin A to Regulate Transcription.

M Behfar Ardehali1, Anthony Anselmo1, Jesse C Cochrane1

  • 1Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

Molecular Cell
|November 21, 2017
PubMed
Summary

Polycomb repressive complex 2 (PRC2) methylates histone H3 and non-histone proteins like Elongin A (EloA). This methylation regulates gene repression and embryonic stem cell differentiation, impacting cancer development.

Keywords:
EZH2Elongin AElongin complexGene repressionPolycomb repressive complex 2 (PRC2)RNA polymerase IISPOT assayprotein methylationtranscription

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Area of Science:

  • Epigenetics and Gene Regulation
  • Molecular Biology
  • Developmental Biology

Background:

  • Polycomb repressive complex 2 (PRC2) is crucial for gene silencing via histone H3 lysine 27 (H3K27) methylation during development.
  • Dysregulation of PRC2 is implicated in various cancers, often linked to aberrant H3K27 methylation.
  • The complete set of non-histone targets for PRC2 and their functional roles remain largely uncharacterized.

Purpose of the Study:

  • To investigate the target recognition specificity of the PRC2 active site.
  • To identify novel non-histone substrates of PRC2.
  • To elucidate the functional consequences of PRC2-mediated methylation of non-histone proteins.

Main Methods:

  • Characterization of PRC2 active site target recognition specificity.
  • Screening for uncharacterized PRC2 targets using specificity data.
  • In vivo methylation analysis of Elongin A (EloA) by PRC2.
  • Assessing the impact of EloA methylation on PRC2 target gene repression and stem cell differentiation.

Main Results:

  • The RNA polymerase II (Pol II) transcription elongation factor, Elongin A (EloA), was identified as a PRC2 substrate in vivo.
  • Mutation of the PRC2-methylated residue on EloA impaired repression of specific PRC2 target genes.
  • Perturbation of EloA methylation affected embryonic stem cell differentiation.
  • PRC2-mediated EloA methylation influences both steady-state and nascent RNA levels of target genes.

Conclusions:

  • PRC2 methylates the non-histone protein Elongin A (EloA).
  • PRC2-mediated EloA methylation plays a role in regulating transcription of a subset of low-expression genes.
  • This mechanism contributes to the maintenance of gene repression and normal embryonic stem cell differentiation.