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.
authors.affiliation: Department of Microbiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: McNamara
authors.affiliation: Department of Microbiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; The University of Texas Southwestern Medical Center School of Medicine, Dallas, TX 75390, USA.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Reeder
authors.affiliation: Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: McMillan
authors.affiliation: Department of Microbiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Curtis W
authors.initials: CW
authors.lastname: Bacon
authors.affiliation: Department of Microbiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: McCann
authors.affiliation: Department of Microbiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: ivan.dorso@utsouthwestern.edu.
authors.forename: Iván
authors.initials: I
authors.lastname: D'Orso
mesh_terms: D001665:Binding Sites; D004789:Enzyme Activation; D015967:Gene Expression Regulation, Viral; D045325:HCT116 Cells; D057809:HEK293 Cells; D006678:HIV / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D046912:Multiprotein Complexes; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D061805:Transcription Elongation, Genetic; D014162:Transfection; D000076183:Tripartite Motif-Containing Protein 28; D014775:Virus Activation
chemical_list: D046912:Multiprotein Complexes; D012097:Repressor Proteins; D017411:Ribonucleoproteins, Small Nuclear; C101116:TRIM28 protein, human; D000076183:Tripartite Motif-Containing Protein 28; D042925:Positive Transcriptional Elongation Factor B; D012319:RNA Polymerase II