UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

The lncRNA HOTAIR impacts on mesenchymal stem cells via triple helix formation

Kalwa, M; Hänzelmann, S; Otto, S; Kuo, CC; Franzen, J; Joussen, S; Fernandez-Rebollo, E; ... Wagner, W; + view all (2016) The lncRNA HOTAIR impacts on mesenchymal stem cells via triple helix formation. Nucleic Acids Research , 44 (22) pp. 10631-10643. 10.1093/nar/gkw802. Green open access

[img]
Preview
Text
Nucl. Acids Res.-2016-Kalwa-10631-43.pdf - ["content_typename_Published version" not defined]

Download (7MB) | Preview

Abstract

There is a growing perception that long non-coding RNAs (lncRNAs) modulate cellular function. In this study, we analyzed the role of the lncRNA HOTAIR in mesenchymal stem cells (MSCs) with particular focus on senescence-associated changes in gene expression and DNA-methylation (DNAm). HOTAIR binding sites were enriched at genomic regions that become hypermethylated with increasing cell culture passage. Overexpression and knockdown of HOTAIR inhibited or stimulated adipogenic differentiation of MSCs, respectively. Modification of HOTAIR expression evoked only very moderate effects on gene expression, particularly of polycomb group target genes. Furthermore, overexpression and knockdown of HOTAIR resulted in DNAm changes at HOTAIR binding sites. Five potential triple helix forming domains were predicted within the HOTAIR sequence based on reverse Hoogsteen hydrogen bonds. Notably, the predicted triple helix target sites for these HOTAIR domains were also enriched in differentially expressed genes and close to DNAm changes upon modulation of HOTAIR Electrophoretic mobility shift assays provided further evidence that HOTAIR domains form RNA-DNA-DNA triplexes with predicted target sites. Our results demonstrate that HOTAIR impacts on differentiation of MSCs and that it is associated with senescence-associated DNAm. Targeting of epigenetic modifiers to relevant loci in the genome may involve triple helix formation with HOTAIR.

Type: Article
Title: The lncRNA HOTAIR impacts on mesenchymal stem cells via triple helix formation
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/nar/gkw802
Publisher version: http://dx.doi.org/10.1093/nar/gkw802
Language: English
Additional information: © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst for Women's Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst for Women's Health > Women's Cancer
URI: http://discovery.ucl.ac.uk/id/eprint/1516720
Downloads since deposit
72Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item