Portoso, M;
Ragazzini, R;
Brencic, Z;
Moiani, A;
Michaud, A;
Vassilev, I;
Wassef, M;
... Margueron, R; + view all
(2017)
PRC2 is dispensable for HOTAIR-mediated transcriptional repression.
EMBO Journal
, 36
(8)
pp. 981-994.
10.15252/embj.201695335.
Preview |
Text
Portoso_PRC2.pdf - Published Version Download (2MB) | Preview |
Abstract
Long non-coding RNAs (lncRNAs) play diverse roles in physiological and pathological processes. Several lncRNAs have been suggested to modulate gene expression by guiding chromatin-modifying complexes to specific sites in the genome. However, besides the example of Xist, clear-cut evidence demonstrating this novel mode of regulation remains sparse. Here, we focus on HOTAIR, a lncRNA that is overexpressed in several tumor types and previously proposed to play a key role in gene silencing through direct recruitment of Polycomb Repressive Complex 2 (PRC2) to defined genomic loci. Using genetic tools and a novel RNA-tethering system, we investigated the interplay between HOTAIR and PRC2 in gene silencing. Surprisingly, we observed that forced overexpression of HOTAIR in breast cancer cells leads to subtle transcriptomic changes that appear to be independent of PRC2. Mechanistically, we found that artificial tethering of HOTAIR to chromatin causes transcriptional repression, but that this effect does not require PRC2. Instead, PRC2 recruitment appears to be a consequence of gene silencing. We propose that PRC2 binding to RNA might serve functions other than chromatin targeting.
| Type: | Article |
|---|---|
| Title: | PRC2 is dispensable for HOTAIR-mediated transcriptional repression |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.15252/embj.201695335 |
| Publisher version: | https://doi.org/10.15252/embj.201695335 |
| Language: | English |
| Additional information: | This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
| Keywords: | chromatin; lincRNA; Polycomb; transcription |
| UCL classification: | UCL 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 > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10061515 |
Loading...
Loading...Loading...Loading...Archive Staff Only
 |
View Item |
