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.
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.
| Original language | English |
|---|---|
| Article number | R98 |
| Journal | Genome Biology |
| Volume | 14 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 17 Sept 2013 |
| Externally published | Yes |