Details

Autor(en) / Beteiligte

• Mondal, Tanmoy
• Subhash, Santhilal
• Vaid, Roshan
• Enroth, Stefan
• Uday, Sireesha
• Reinius, Björn
• Mitra, Sanhita
• Mohammed, Arif
• James, Alva Rani
• Hoberg, Emily
• Moustakas, Aristidis
• Gyllensten, Ulf
• Jones, Steven J M
• Gustafsson, Claes M
• Sims, Andrew H
• Westerlund, Fredrik
• Gorab, Eduardo
• Kanduri, Chandrasekhar

Titel

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

Ist Teil von

• Nature communications, 2015-07, Vol.6 (1), p.7743-7743, Article 7743

Ort / Verlag

England: Nature Pub. Group

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.