MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA–DNA triplex structures
Journal article, 2015

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.

'Long non coding RNAs'

'MEG3'

'noncoding'

Author

Tanmoy Mondal

University of Gothenburg

Santhilal Subhash

University of Gothenburg

Roshan Vaid

University of Gothenburg

Stefan Enroth

Uppsala University

Sireesha Uday

University of Gothenburg

Björn Reinius

University of Gothenburg

Sanhita Mitra

University of Gothenburg

Arif Mohammed

University of Gothenburg

Alva Rani James

University of Gothenburg

Emily Hoberg

University of Gothenburg

Aristidis Moustakas

Uppsala University

Ulf Gyllensten

Uppsala University

Steven J.M. Jones

British Columbia Cancer Agency

Claes M Gustafsson

University of Gothenburg

Andrew H Sims

University of Edinburgh

Fredrik Westerlund

Chalmers, Biology and Biological Engineering, Chemical Biology

Eduardo Gorab

University of Sao Paulo (USP)

Chandrasekhar Kanduri

University of Gothenburg

Nature Communications

2041-1723 (ISSN)

Vol. 6 art no. 7743- 8743

Subject Categories

Basic Medicine

Biochemistry and Molecular Biology

Medical Engineering

Areas of Advance

Nanoscience and Nanotechnology (2010-2017)

Life Science Engineering (2010-2018)

DOI

10.1038/ncomms8743

PubMed

26205790

More information

Latest update

2/28/2018