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The non-coding snRNA 7SK controls transcriptional termination, poising, and bidirectionality in embryonic stem cells

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Peer-reviewed

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Article

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Authors

Castelo-Branco, G 
De Paiva Rosa Amaral, Paulo  ORCID logo  https://orcid.org/0000-0002-6696-5142
Engström, PG 
Robson, S 
Marques, SC 

Abstract

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.

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Journal Title

Genome Biology

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Journal ISSN

Volume Title

14

Publisher

BioMed Central
Sponsorship
European Research Council (268569)
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).