Genome-wide analysis of KAP1, the 7SK snRNP complex, and RNA polymerase II

McNamara, Ryan P.; Guzmán, Carlos; Reeder, Jonathan E.; D’Orso, Iván

doi:10.1016/j.gdata.2016.01.019

Cited by 11 publications

(8 citation statements)

References 16 publications

(22 reference statements)

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“…TIF1␤ is also known as TRIM28 and KAP1 and was recently described as a factor participating in pol II pausing on the human HSPA1B promoter (27). A subsequent analysis suggested similar functions (28,63). We have elected to use the TIF1␤ designation to emphasize the relationship to elongation, as TIF1␥ also has elongation properties, including recruiting P-TEFb to promoters (64,65).…”

Section: Discussionmentioning

confidence: 99%

O-GlcNAcase Is an RNA Polymerase II Elongation Factor Coupled to Pausing Factors SPT5 and TIF1β

Resto

Kim

Fernandez

et al. 2016

Journal of Biological Chemistry

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We describe here the identification and functional characterization of the enzyme O-GlcNAcase (OGA) as an RNA polymerase II elongation factor. Using in vitro transcription elongation assays, we show that OGA activity is required for elongation in a crude nuclear extract system, whereas in a purified system devoid of OGA the addition of rOGA inhibited elongation. Furthermore, OGA is physically associated with the known RNA polymerase II (pol II) pausing/elongation factors SPT5 and TRIM28-KAP1-TIF1␤, and a purified OGA-SPT5-TIF1␤ complex has elongation properties. Lastly, ChIP-seq experiments show that OGA maps to the transcriptional start site/5 ends of genes, showing considerable overlap with RNA pol II, SPT5, TRIM28-KAP1-TIF1␤, and O-GlcNAc itself. These data all point to OGA as a component of the RNA pol II elongation machinery regulating elongation genome-wide. Our results add a novel and unexpected dimension to the regulation of elongation by the insertion of O-GlcNAc cycling into the pol II elongation regulatory dynamics.RNA polymerase II is the species of polymerase that transcribes the protein-coding genes in the cell. Largely based on in vitro transcription data and bacterial transcriptional regulation, it was thought that the pathway of transcription initiation was the de novo assembly and recruitment of general factors and pol II 4 into a preinitiation complex at promoters. In other words, transcription was solely controlled by whether initiation occurred or not. However, in the late 1980s, a transcriptionally engaged pol II was found on several genes, located roughly at ϩ50 relative to the transcriptional start site (TSS) (1-3). More recently, genome-wide approaches have shown that paused pol II exists on at least 40% of promoters in the genome (4 -9).These data show that the regulation of elongation is a significant and widespread method by which cells regulate gene expression.Biochemically, the establishment of a paused polymerase requires the recruitment of DSIF and NELF to pol II early in elongation to prevent pol II from productive elongation (10 -13). Release of the paused polymerase is achieved with P-TEFb phosphorylation of DSIF and NELF, ejecting NELF from pol II and converting DSIF into a positive elongation factor (14,15). The more recent discoveries of additional factors likely involved in pause establishment and release include human capping enzyme (16), the TFIIH-associated kinase, CDK7 (17, 18), the TFIIH ERCC3 helicase (19), , Integrator (23,24), ELL (25), TFIIS (26), TRIM28-KAP1-TIF1␤ (27, 28), Top1 (29), SEC (30), PAF complex (31, 32), and Gdown1 (33). The plethora of factors suggests that more complicated dynamics are at play in regulating pausing and elongation. Additionally, it is not clear, and indeed difficult to know, whether all of the factors involved in pol II pausing and elongation have been identified. This difficulty is due mostly to the absence of a human cell-based in vitro transcription system that recapitulates a paused polymerase and with which the full complement of...

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Section: Discussionmentioning

confidence: 99%

O-GlcNAcase Is an RNA Polymerase II Elongation Factor Coupled to Pausing Factors SPT5 and TIF1β

Resto

Kim

Fernandez

et al. 2016

Journal of Biological Chemistry

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“…and tether 7SK snRNP to the promoters of primary response genes (PRGs) in respond to stimuli. 23,24 Genome-wide studies showed that KAP1 and 7SK snRNP co-localized on most promoters containing paused Pol II. 23 Depletion of KAP1 reduced the promoter occupancy of 7SK snRNP and impeded the transcription elongation.…”

Section: The Non-canonical P-tefb Recruitment Modelmentioning

confidence: 99%

“…23,24 Genome-wide studies showed that KAP1 and 7SK snRNP co-localized on most promoters containing paused Pol II. 23 Depletion of KAP1 reduced the promoter occupancy of 7SK snRNP and impeded the transcription elongation. 24 However, how P-TEFb is released from 7SK snRNP "on-site" in this case remains unknown.…”

Section: The Non-canonical P-tefb Recruitment Modelmentioning

confidence: 99%

“…11,[16][17][18] Of interest, while the active P-TEFb has been proposed to be the major form that is inducibly recruited to gene promoters upon stimulation, several recent studies showed that the inactive P-TEFb in the 7SK snRNA complex can also be loaded onto a vast array of promoters for the release of paused Pol II either in basal or stimulation state. [22][23][24] Although the recruitment of inactive 7SK snRNP and the release of P-TEFb at promoter employ very diverse mechanisms, nevertheless, it represents another approach to release the promoter-proximally paused Pol II. To distinguish these two distinct recruitment mechanisms, we refer to the recruitment of active form of P-TEFb as the canonical P-TEFb recruitment model and the recruitment of inactive P-TEFb in complex with 7SK snRNP as the non-canonical P-TEFb recruitment model.…”

Section: Introductionmentioning

confidence: 99%

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P-TEFb: Finding its ways to release promoter-proximally paused RNA polymerase II

Liu

Chen

et al. 2018

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“…KAP1 interacts directly with the 7SK snRNP subunit LARP7 to pre-load the inactive P-TEFb to the promoter-proximal region, which upon stimulation facilitates a rapid transition of the paused RNAPII to productive transcription elongation [55]. This phenomenon was absent from both fully transcriptionally active genes and totally inactive genes [55, 56]. This mechanism, estimated to be specific to up to 70% of genes with promoter-proximal paused RNAPII, was first demonstrated at the HIV promoter [55].…”

Section: Early Events In Tat-mediated Hiv-1 Transcriptionmentioning

confidence: 99%

Role of Host Factors on the Regulation of Tat-Mediated HIV-1 Transcription

Mousseau

Valente

2017

CPD

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Background The viral transactivator Tat protein is a key modulator of HIV-1 replication, as it regulates transcriptional elongation from the integrated proviral genome. Tat recruits the human transcription elongation factor b, and other host proteins, such as the super elongation complex, to activate the cellular RNA polymerase II, normally stalled shortly after transcription initiation at the HIV promoter. By means of a complex set of interactions with host cellular factors, Tat determines the fate of viral activity within the infected cell. The virus will either actively replicate to promote dissemination in blood and tissues, or become dormant mostly in memory CD4+ T cells, as part of a small but long-living latent reservoir, the main obstacle for HIV eradication. Objective In this review, we summarize recent advances in the understanding of the multi-step mechanism that regulates Tat-mediated HIV-1 transcription and RNA polymerase II release, to promote viral transcription elongation. Early events of the human transcription elongation factor b release from the inhibitory 7SK small nuclear ribonucleoprotein complex and its recruitment to the HIV promoter will be discussed. Specific roles of the super elongation complex subunits during transcription elongation, and insight on recently identified cellular factors and mechanisms regulating HIV latency will be detailed. Conclusion Understanding the complexity of HIV transcriptional regulation by host factors may open the door for development of novel strategies to eradicate the resilient latent reservoir.

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Genome-wide analysis of KAP1, the 7SK snRNP complex, and RNA polymerase II

Cited by 11 publications

References 16 publications

O-GlcNAcase Is an RNA Polymerase II Elongation Factor Coupled to Pausing Factors SPT5 and TIF1β

O-GlcNAcase Is an RNA Polymerase II Elongation Factor Coupled to Pausing Factors SPT5 and TIF1β

P-TEFb: Finding its ways to release promoter-proximally paused RNA polymerase II

Role of Host Factors on the Regulation of Tat-Mediated HIV-1 Transcription

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