MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures

Nat Commun. 2015 Jul 24;6:7743. doi: 10.1038/ncomms8743.

Abstract

Long noncoding RNAs (lncRNAs) regulate gene expression by association with chromatin, but how they target chromatin remains poorly understood. We have used chromatin RNA immunoprecipitation-coupled high-throughput sequencing to identify 276 lncRNAs enriched in repressive chromatin from breast cancer cells. Using one of the chromatin-interacting lncRNAs, MEG3, we explore the mechanisms by which lncRNAs target chromatin. Here we show that MEG3 and EZH2 share common target genes, including the TGF-β pathway genes. Genome-wide mapping of MEG3 binding sites reveals that MEG3 modulates the activity of TGF-β genes by binding to distal regulatory elements. MEG3 binding sites have GA-rich sequences, which guide MEG3 to the chromatin through RNA-DNA triplex formation. We have found that RNA-DNA triplex structures are widespread and are present over the MEG3 binding sites associated with the TGF-β pathway genes. Our findings suggest that RNA-DNA triplex formation could be a general characteristic of target gene recognition by the chromatin-interacting lncRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • DNA / metabolism
  • Enhancer of Zeste Homolog 2 Protein
  • Gene Expression Regulation*
  • Humans
  • Polycomb Repressive Complex 2 / metabolism
  • RNA, Long Noncoding / metabolism*
  • Transforming Growth Factor beta / metabolism

Substances

  • MEG3 non-coding RNA, human
  • RNA, Long Noncoding
  • Transforming Growth Factor beta
  • triplex DNA
  • DNA
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2