Journal
MOLECULAR CELL
Volume 61, Issue 1, Pages 39-53Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2015.11.004
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Funding
- National Institute of Allergy and Infectious Diseases of the NIH [R56AI106514, R01AI114362]
- Welch Foundation [I-1782]
- NIH [2T32AI007520-16, 5T32GM8203-27]
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The transition from transcription initiation to elongation at promoters of primary response genes (PRGs) in metazoan cells is controlled by inducible transcription factors, which utilize P-TEFb to phosphorylate RNA polymerase II (Pol II) in response to stimuli. Prior to stimulation, a fraction of P-TEFb is recruited to promoter-proximal regions in a catalytically inactive state bound to the 7SK small nuclear ribonucleoprotein (snRNP) complex. However, it remains unclear how and why the 7SK snRNP is assembled at these sites. Here we report that the transcriptional regulator KAP1 continuously tethers the 7SK snRNP to PRG promoters to facilitate P-TEFb recruitment and productive elongation in response to stimulation. Remarkably, besides PRGs, genome-wide studies revealed that KAP1 and 7SK snRNP co-occupy most promoter-proximal regions containing paused Pol II. Collectively, we provide evidence of an un-precedented mechanism controlling 7SK snRNP delivery to promoter-proximal regions to facilitate on-site'' P-TEFb activation and Pol II elongation.
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