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

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

Author information

1
Department of Medical Genetics, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, SE-40530 Gothenburg, Sweden.
2
Department of Immunology, Genetics and Pathology, Biomedical Center, SciLifeLab Uppsala, Uppsala University, SE-75108 Uppsala, Sweden.
3
Department of Medical Biochemistry and Cell Biology, University of Gothenburg, PO Box 440, SE-405 30 Gothenburg, Sweden.
4
1] Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, PO Box 582, SE-751 23 Uppsala, Sweden [2] Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University, PO Box 595, SE-751 24 Uppsala, Sweden.
5
Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia BC V5Z 4S6, Canada.
6
Applied Bioinformatics of Cancer, University of Edinburgh Cancer Research UK Centre, Edinburgh EH4 2XR, UK.
7
Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg 412 96, Sweden.
8
Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo CEP:05508-090, Brazil.

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.

PMID:
26205790
PMCID:
PMC4525211
DOI:
10.1038/ncomms8743
[Indexed for MEDLINE]
Free PMC Article

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