Abstract:
: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 unprecedented mechanism controlling 7SK snRNP delivery to promoter-proximal regions to facilitate "on-site" P-TEFb activation and Pol II elongation.
journal_name
Mol Celljournal_title
Molecular cellauthors
McNamara RP,Reeder JE,McMillan EA,Bacon CW,McCann JL,D'Orso Idoi
10.1016/j.molcel.2015.11.004subject
Has Abstractpub_date
2016-01-07 00:00:00pages
39-53issue
1eissn
1097-2765issn
1097-4164pii
S1097-2765(15)00864-3journal_volume
61pub_type
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