Genome-wide identification of Polycomb-associated RNAs by RIP-seq

By Toshiro K. Ohsumi, Johnny T Y Kung, Y. Ogawa, D. Grau, K. Sarma, J. Song, Robert E. Kingston, Mark L. Borowsky, Jeannie T. Lee. Molecules and Cells, 2010

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SUMMARY 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 >9,000 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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ec030f35c3e1e86216514b360a06800792a7a327

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Citations in the corpus

Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs (2012, background): “Since numerous lncRNAs are known to bind to chromatin-modifying complexes (4,74), it is conceivable that many of these lncRNAs also function by ‘guiding’ their protein partners to chromatin.”
Long Noncoding RNAs: Past, Present, and Future (2013, background): “Some of these lncRNAs may function by recruiting epigenetic factors, such as PRC2 and G9a, to control the imprinted expression of neighboring coding genes (Nagano et al. 2008; Pandey et al. 2008; Zhao et al. 2010).”
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Transcriptional regulation by Polycomb group proteins (2013, background): “; and from the Novo Nordisk Foundation, the Danish Cancer Society and the Danish Council for Strategic Research (12-110503) to K.”
Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis. (2012, background): “…have been shown to interact with and modulate the activity of the chromatin modifying machinery (Rinn et al. 2007; Nagano et al. 2008; Pandey et al. 2008; Zhao et al. 2008, 2010; Khalil et al. 2009; Huarte et al. 2010; Tian et al. 2010; Tsai et al. 2010; Guttman et al. 2011; Wang et al. 2011).”
Long noncoding RNAs: Cellular address codes in development and disease (2013, neutral): “Several such lncRNAs are now recognized to interact with and recruit histone modification complexes, including Xist (recruits PRC2 for H3K27me3 and RYBP-PRC1 for H2A ubiquitylation) and Kcnq1ot1 (recruits G9a for H3K9me3 and PRC2) (Pandey et al., 2008; Tavares et al., 2012; Zhao et al., 2010).”
The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse (2013, background): “It has been shown that components of both the PRC2 and TrxG/MLL complexes are able to interact with long noncoding RNAs (lncRNAs) (Zhao et al., 2008, 2010; Wang et al., 2011).”
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The Landscape of long non-coding RNA classification (2015, neutral): “Within the nucleus, ncRNA association with, and targeting of, the gene-silencing PRC2 complex led to the identification of thousands of PRC2-associated ncRNAs in mouse embryonic stem cells [103] and human cell lines [19].”