Nat. Struct. Mol. Biol., doi:10.1038/nsmb.2679;

Nat. Struct. Mol. Biol., doi:10.1038/nsmb.2700

Pervasive genomic transcription produces abundant coding and noncoding RNAs, the functional roles of which remain largely uncharacterized. Two recent studies suggest a new link between transcriptional and epigenetic regulation that is mediated by direct binding of RNA transcripts to a histone methyltransferase complex. In the first study, Davidovich et al. showed that the polycomb repressive complex 2 (PRC2), which installs repressive methyl marks on Lys27 of histone 3 (H3K27), binds diverse RNAs in vitro and in cells, with a preference for longer transcripts. The authors' analysis of transcriptomic data suggests that PRC2 is localized to repressed genes, but it is also surprisingly associated with active genes that are not typically repressed by PRC2. On this basis, the authors suggest that promiscuous binding of RNA transcripts by PRC2 recruits PRC2 to maintain repressed chromatin. In the second study, Kaneko et al. also observe that PRC2 is associated with active chromatin by applying a cross-linking approach to identify RNA-protein interactions within embryonic stem cells. They show that EZH2, the methyltransferase component of PRC2, interacts preferentially with 5′-terminal regions of numerous transcripts. These ezRNAs arise from genes that are not regulated by PRC2 and that are depleted in H3K27me3 marks. Their model suggests that ezRNA-PRC2 interactions sense transcriptional status and that changes in ezRNA expression during differentiation may restore PRC2 repressive activity. Taken together, these two studies provide further evidence that broad-based transcription is harnessed for subtle gene regulatory pathways.