PRC2 Recruitment to Target Genes Via Non-Coding RNAs

描述（由申请人提供）：多梳抑制复合物2（PRC2）向靶基因的募集一直是染色质领域非常感兴趣的主题。尽管许多实验室做出了努力，但尚不完全清楚这种发育必需的复合物如何实现靶特异性。近年来引起广泛关注的一个想法是发现非编码RNA（ncRNA）可以将PRC2引导到染色质上的特定位点。在其他几个辅助和核心成分中的RNA结合区（RBRs）的最终鉴定提高了ncRNA可能介导PRC2募集的可能性。在这个提议中，我将研究这些ncRNA之一，即MEG3的功能，它被发现与辅助蛋白JARID2结合。该提议的生物学相关性是观察到MEG3 ncRNA与基因簇的异常沉默相关，所述基因簇在诱导多能性干细胞（iPSC）的分化中是重要的。因此，iPSC衍生疗法的真正潜力由于这种效应而受到阻碍。该提案的发现将深入了解RNA和蛋白质之间的复杂相互作用，并提供PRC2招募靶基因的机制。

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.