KAP1 Recruitment of the 7SK snRNP Complex to Promoters Enables Transcription Elongation by RNA Polymerase II
| Autor: | Elizabeth A. McMillan, Jennifer L. McCann, Ryan P. McNamara, Curtis W. Bacon, Iván D'Orso, Jonathan E. Reeder |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Gene Expression Regulation Viral Time Factors Transcription Elongation Genetic Positive Transcriptional Elongation Factor B RNA polymerase II Tripartite Motif-Containing Protein 28 Transfection Article 03 medical and health sciences Jurkat Cells 7SK RNA Transcriptional regulation Humans snRNP Promoter Regions Genetic Molecular Biology Ribonucleoprotein Binding Sites biology HIV Promoter Cell Biology HCT116 Cells Ribonucleoproteins Small Nuclear Molecular biology Cell biology Enzyme Activation Repressor Proteins 030104 developmental biology HEK293 Cells Multiprotein Complexes biology.protein RNA Interference Virus Activation RNA Polymerase II Small nuclear ribonucleoprotein |
| Popis: | SummaryThe 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. |
| Databáze: | OpenAIRE |
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