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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

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

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. More... »

PAGES

7743

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms8743

DOI

http://dx.doi.org/10.1038/ncomms8743

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1050382180

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26205790


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452 schema:name Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia BC V5Z 4S6, Canada
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454 https://www.grid.ac/institutes/grid.470904.e schema:alternateName Edinburgh Cancer Research Centre
455 schema:name Applied Bioinformatics of Cancer, University of Edinburgh Cancer Research UK Centre, Edinburgh EH4 2XR, UK
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458 schema:name Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg 412 96, Sweden
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460 https://www.grid.ac/institutes/grid.8761.8 schema:alternateName University of Gothenburg
461 schema:name Department of Medical Biochemistry and Cell Biology, University of Gothenburg, PO Box 440, SE-405 30 Gothenburg, Sweden
462 Department of Medical Genetics, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, SE-40530 Gothenburg, Sweden
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464 https://www.grid.ac/institutes/grid.8993.b schema:alternateName Uppsala University
465 schema:name Department of Immunology, Genetics and Pathology, Biomedical Center, SciLifeLab Uppsala, Uppsala University, SE-75108 Uppsala, Sweden
466 Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, PO Box 582, SE-751 23 Uppsala, Sweden
467 Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University, PO Box 595, SE-751 24 Uppsala, Sweden
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