MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA–DNA triplex structures
Artikel i vetenskaplig tidskrift, 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'

Författare

Tanmoy Mondal

Göteborgs universitet

Santhilal Subhash

Göteborgs universitet

Roshan Vaid

Göteborgs universitet

Stefan Enroth

Uppsala universitet

Sireesha Uday

Göteborgs universitet

Björn Reinius

Göteborgs universitet

Sanhita Mitra

Göteborgs universitet

Arif Mohammed

Göteborgs universitet

Alva Rani James

Göteborgs universitet

Emily Hoberg

Göteborgs universitet

Aristidis Moustakas

Uppsala universitet

Ulf Gyllensten

Uppsala universitet

Steven J.M. Jones

British Columbia Cancer Agency

Claes M Gustafsson

Göteborgs universitet

Andrew H Sims

University of Edinburgh

Fredrik Westerlund

Chalmers, Biologi och bioteknik, Kemisk biologi

Eduardo Gorab

Universidade de Sao Paulo (USP)

Chandrasekhar Kanduri

Göteborgs universitet

Nature Communications

2041-1723 (ISSN)

Vol. 6 art no. 7743- 8743

Ämneskategorier

Medicinska grundvetenskaper

Biokemi och molekylärbiologi

Medicinteknik

Styrkeområden

Nanovetenskap och nanoteknik

Livsvetenskaper och teknik

DOI

10.1038/ncomms8743

PubMed

26205790

Mer information

Senast uppdaterat

2018-02-28