Many lncRNAs are thought to interact with the polycomb repressive complex 2 (PRC2) in order to regulate gene expression. A central example of this lncRNA–PRC2 paradigm in gene regulation is HOTAIR. In this issue of The EMBO Journal, a study (Portoso et al, 2017) reports that while HOTAIR binds PRC2 with high affinity, the complex itself is dispensable for HOTAIR‐mediated transcriptional silencing. This study raises important questions about the role of PRC2 interactions for lncRNA‐mediated functions and argues for a re‐evaluation of this lncRNA–PRC2 functional paradigm.
See also: M Portoso et al
The polycomb repressive complex 2 (PRC2) is a critical chromatin regulatory complex that plays an important role in transcriptional silencing in various biological contexts. Over the past decade, there has been enormous interest in the role of PRC2 and its interaction with various long non‐coding RNAs (lncRNAs). This excitement derives primarily from the discovery that the Xist and HOTAIR lncRNAs silence transcription, physically interact with the PRC2 complex, and that perturbation of these RNAs impacts PRC2 localization at their target sites (Rinn et al, 2007; Zhao et al, 2008). Based on these observations, numerous studies have uncovered hundreds of lncRNAs that interact with PRC2 (Khalil et al, 2009; Zhao et al, 2010). Since PRC2 in mammals lacks clear DNA sequence specificity, these results led to a model whereby lncRNAs guide PRC2 to specific targets on DNA to control chromatin modification and gene expression.
However, there are several emerging challenges to this model. Recent studies have shown that PRC2 components interact …
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