PRC2 Recruitment to Target Genes Via Non-Coding RNAs

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DESCRIPTION (provided by applicant): Recruitment of the Polycomb Repressive Complex 2 (PRC2) to target genes has been the topic of a lot of interest in the chromatin field. Despite the efforts by many labs, it is not entirely clear how such a developmentally essential complex achieves target specificity. One idea that has attracted much attention in recent years was the discovery that non-coding RNAs (ncRNAs) can direct PRC2 at specific sites on chromatin. The eventual identification of RNA binding regions (RBRs) in several other accessory and core components raised the possibility that ncRNAs may mediate PRC2 recruitment. In this proposal, I will investigate the function of one of these ncRNAs, namely MEG3, which was found to bind to the accessory protein JARID2. The biological relevance of this proposal is the observation that MEG3 ncRNA is associated with aberrant silencing of gene clusters that are important in differentiation of induced pluripotency stem cells (iPSCs). Thus, the true potential of iPSC-derived therapies has hampered due to this effect. The findings from this proposal will shed insight into the complex interactions between RNA and protein, and provide a mechanism of PRC2 recruitment to target genes.