Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Mol Cell. 2010 Dec 22;40(6):939-53. doi: 10.1016/j.molcel.2010.12.011.
Polycomb proteins play essential roles in stem cell renewal and human disease. Recent studies of HOX genes and X inactivation have provided evidence for RNA cofactors in Polycomb repressive complex 2 (PRC2). Here we develop a RIP-seq method to capture the PRC2 transcriptome and identify a genome-wide pool of >9000 PRC2-interacting RNAs in embryonic stem cells. The transcriptome includes antisense, intergenic, and promoter-associated transcripts, as well as many unannotated RNAs. A large number of transcripts occur within imprinted regions, oncogene and tumor suppressor loci, and stem cell-related bivalent domains. We provide evidence for direct RNA-protein interactions, most likely via the Ezh2 subunit. We also identify Gtl2 RNA as a PRC2 cofactor that directs PRC2 to the reciprocally imprinted Dlk1 coding gene. Thus, Polycomb proteins interact with a genome-wide family of RNAs, some of which may be used as biomarkers and therapeutic targets for human disease.
多梳蛋白在干细胞更新和人类疾病中发挥着重要作用。最近对 HOX 基因和 X 染色体失活的研究为多梳抑制复合物 2（PRC2）中的 RNA 辅助因子提供了证据。在这里，我们开发了一种 RIP-seq 方法来捕获 PRC2 转录组，并在胚胎干细胞中鉴定了 >9000 个全基因组的 PRC2 相互作用 RNA。该转录组包括反义、基因间和启动子相关转录本，以及许多未注释的 RNA。大量转录本发生在印迹区域、癌基因和肿瘤抑制基因座以及与干细胞相关的二价结构域内。我们提供了直接的 RNA-蛋白质相互作用的证据，最有可能是通过 Ezh2 亚基。我们还鉴定了 Gtl2 RNA 作为 PRC2 的辅助因子，它将 PRC2 导向相互印迹的 Dlk1 编码基因。因此，多梳蛋白与全基因组范围内的 RNA 家族相互作用，其中一些 RNA 可能被用作人类疾病的生物标志物和治疗靶点。
