The non-coding snRNA 7SK controls transcriptional termination, poising, and bidirectionality in embryonic stem cells
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Castelo-Branco, G., De Paiva Rosa Amaral, P., Engström, P., Robson, S., Marques, S., Bertone, P., & Kouzarides, T. (2013). The non-coding snRNA 7SK controls transcriptional termination, poising, and bidirectionality in embryonic stem cells. Genome Biology, 14 (R98)https://doi.org/10.1186/gb-2013-14-9-r98
BACKGROUND: Pluripotency is characterized by a unique transcriptional state, in which lineage-specification genes are poised for transcription upon exposure to appropriate stimuli, via a bivalency mechanism involving the simultaneous presence of activating and repressive methylation marks at promoter-associated histones. Recent evidence suggests that other mechanisms, such as RNA polymerase II pausing, might be operational in this process, but their regulation remains poorly understood. RESULTS: Here we identify the non-coding snRNA 7SK as a multifaceted regulator of transcription in embryonic stem cells. We find that 7SK represses a specific cohort of transcriptionally poised genes with bivalent or activating chromatin marks in these cells, suggesting a novel poising mechanism independent of Polycomb activity. Genome-wide analysis shows that 7SK also prevents transcription downstream of polyadenylation sites at several active genes, indicating that 7SK is required for normal transcriptional termination or control of 3′-UTR length. In addition, 7SK suppresses divergent upstream antisense transcription at more than 2,600 loci, including many that encode divergent long non-coding RNAs, a finding that implicates the 7SK snRNA in the control of transcriptional bidirectionality. CONCLUSIONS: Our study indicates that a single non-coding RNA, the snRNA 7SK, is a gatekeeper of transcriptional termination and bidirectional transcription in embryonic stem cells and mediates transcriptional poising through a mechanism independent of chromatin bivalency.
GCB was funded by an EMBO Long-Term Post-Doctoral Fellowship and a Marie Curie Intra-European Fellowship for Career Development. PA was supported by a Royal Society Newton International Fellowship and a Corpus Christi College research fellowship. This work was supported by Cancer Research UK, European Research Council (Advanced Grant, TK), EMBL (PB) and Swedish Research Council (GCB).
European Research Council (268569)
External DOI: https://doi.org/10.1186/gb-2013-14-9-r98
This record's URL: https://www.repository.cam.ac.uk/handle/1810/286039
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/