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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Mondal T,Subhash S,Vaid R,Enroth S,Uday S,Reinius B,Mitra S,Mohammed A,James AR,Hoberg E,Moustakas A,Gyllensten U,Jones SJ,Gustafsson CM,Sims AH,Westerlund F,Gorab E,Kanduri Cdoi
10.1038/ncomms8743subject
Has Abstractpub_date
2015-07-24 00:00:00pages
7743issn
2041-1723pii
ncomms8743journal_volume
6pub_type
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