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Nat Commun ; 6: 7743, 2015 Jul 24.
Article in English | MEDLINE | ID: mdl-26205790

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-ß pathway genes. Genome-wide mapping of MEG3 binding sites reveals that MEG3 modulates the activity of TGF-ß 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-ß pathway genes. Our findings suggest that RNA-DNA triplex formation could be a general characteristic of target gene recognition by the chromatin-interacting lncRNAs.


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