The long noncoding RNA Gm15055 represses Hoxa gene expression by recruiting PRC2 to the gene cluster.

TheHoxgenes encode transcription factors that determine embryonic pattern formation. In embryonic stem cells, theHoxgenes are silenced by PRC2. Recent studies have reported a role for long noncoding RNAs in PRC2 recruitment in vertebrates. However, little is known about how PRC2 is recruited to theHoxgenes in ESCs. Here, we used stable knockdown and knockout strategies to characterize the function of the long noncoding RNAGm15055in the regulation ofHoxagenes in mouse ESCs. We found thatGm15055is highly expressed in mESCs and its expression is maintained by OCT4.Gm15055repressesHoxagene expression by recruiting PRC2 to the cluster and maintaining the H3K27me3 modification onHoxapromoters. A chromosome conformation capture assay revealed the close physical association of theGm15055locus to multiple sites at theHoxagene cluster in mESCs, which may facilitate thein cistargeting ofGm15055RNA to theHoxagenes. Furthermore, an OCT4-responsive positivecis-regulatory element is found in theGm15055gene locus, which potentially regulates bothGm15055itself and theHoxagene activation. This study suggests how PRC2 is recruited to theHoxalocus in mESCs, and implies an elaborate mechanism forHoxagene regulation in mESCs.

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