@article{338697a3d6c5452cae360ea2f9f24424,
title = "KAP1 Recruitment of the 7SK snRNP Complex to Promoters Enables Transcription Elongation by RNA Polymerase II",
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. McNamara et al. use a combination of biochemical approaches to identify KAP1 as an interactor of the 7SK snRNP complex. Using genomics, they found that the KAP1-7SK snRNP complex is recruited to most promoter-proximal regions containing paused RNA polymerase II to facilitate {"}on-site{"} P-TEFb activation and transcriptional pause release.",
author = "McNamara, {Ryan P.} and Reeder, {Jonathan E.} and McMillan, {Elizabeth A.} and Bacon, {Curtis W.} and McCann, {Jennifer L.} and Iv{\'a}n D'Orso",
note = "Funding Information: We thank T. Kim and N. Conrad for critical reading of this manuscript; the UT Southwestern Proteomics and Live Cell Imaging cores for their assistance with protein identification and high-resolution microscopy, respectively; J. Espinosa for sharing and providing advice on GRO-seq; and C. Guzman for computational support. We are grateful to J. Karn for generously sharing the Jurkat HIV E4, 2B2D, and 2B5 clones. The 6.3, 8.4, and 9.2 Jurkat HIV clones were obtained from the NIH AIDS Reagent Program kindly deposited by E. Verdin. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the NIH under award numbers R56AI106514 and R01AI114362, and Welch Foundation grant I-1782 (to I.D.). R.P.M. was supported by NIH training grant 2T32AI007520-16. C.W.B. and E.A.M. were supported by NIH training grant 5T32GM8203-27. Funding Information: We thank T. Kim and N. Conrad for critical reading of this manuscript; the UT Southwestern Proteomics and Live Cell Imaging cores for their assistance with protein identification and high-resolution microscopy, respectively; J. Espinosa for sharing and providing advice on GRO-seq; and C. Guzman for computational support. We are grateful to J. Karn for generously sharing the Jurkat HIV E4, 2B2D, and 2B5 clones. The 6.3, 8.4, and 9.2 Jurkat HIV clones were obtained from the NIH AIDS Reagent Program kindly deposited by E. Verdin. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the NIH under award numbers R56AI106514 and R01AI114362, and Welch Foundation grant I-1782 (to I.D.). R.P.M. was supported by NIH training grant 2T32AI007520-16. C.W.B. and E.A.M. were supported by NIH training grant 5T32GM8203-27. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = jan,
day = "7",
doi = "10.1016/j.molcel.2015.11.004",
language = "English (US)",
volume = "61",
pages = "39--53",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "1",
}