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MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. (Gyllensten)ORCID iD: 0000-0002-5056-9137
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2015 (English)In: Nature Communications, ISSN 2041-1723, Vol. 6, 7743Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2015. Vol. 6, 7743
National Category
Medical Genetics
URN: urn:nbn:se:uu:diva-259481DOI: 10.1038/ncomms8743ISI: 000358858500049PubMedID: 26205790OAI: oai:DiVA.org:uu-259481DiVA: diva2:844331
Knut and Alice Wallenberg Foundation, AW 2014.0057Swedish Cancer Society, 140317Swedish Research Council, K2014-67X-20781-07-4Swedish Childhood Cancer Foundation, PR2014/0147
Available from: 2015-08-05 Created: 2015-08-05 Last updated: 2015-09-01Bibliographically approved

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Enroth, StefanMoustakas, AristidisGyllensten, Ulf
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Medicinsk genetik och genomikScience for Life Laboratory, SciLifeLabDepartment of Medical Biochemistry and MicrobiologyLudwig Institute for Cancer Research
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