PRC2 is dispensable for HOTAIR‐mediated transcriptional repression

• Manuela Portoso ^[2] ; Roberta Ragazzini ^[2] ; Živa Brenčič ^[2] ; Arianna Moiani ^[2] ; Audrey Michaud ^[2] ; Ivaylo Vassilev ^[2] ; Michel Wassef ^[2] ; Nicolas Servant ^[3] ; Bruno Sargueil ^[1] ; Raphaël Margueron ^[2]
  1. [1] Paris Descartes University

     Paris Descartes University

     París, Francia

     
  2. [2] 1 Institut Curie PSL Research University Paris France; 2 INSERM U934 CNRS UMR3215 Paris France
  3. [3] 1 Institut Curie PSL Research University Paris France; 3 INSERM U900 Mines ParisTech Paris France

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 36, Nº. 8, 2017, págs. 981-994
• Idioma: inglés
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  • 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.