Genetic and Genomic Analyses of RNA Polymerase II-pausing Factor in Regulation of Mammalian Transcription and Cell Growth

Sun, Jie; Pan, Haihui; Lei, Chengwei; Yuan, Bin; Nair, Sreejith J.; April, Craig; Parameswaran, Balaji; Klotzle, Brandy; Fan, Jie; Ruan, Jianhua; Li, Rong

doi:10.1074/jbc.m111.269167

Cited by 25 publications

(37 citation statements)

References 50 publications

(72 reference statements)

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“…3). On the beta-actin gene, the normalized NELF signal around the TSS was higher than the corresponding signal at þ 300, which agrees with recent genome-wide NELF-binding studies showing that peak binding of this protein occurs close to the TSS 35,36 . Conversely, the normalized NELF signal around the TSS of the U1 gene was lower than the signals at positions þ 180 and þ 370 ( Supplementary Fig.…”

Section: Dsif and Nelf Interact With Integrator Via Spt5 And Nelf-asupporting

confidence: 89%

DSIF and NELF interact with Integrator to specify the correct post-transcriptional fate of snRNA genes

et al. 2014

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The elongation factors DSIF and NELF are responsible for promoter-proximal RNA polymerase II (Pol II) pausing. NELF is also involved in 3' processing of replication-dependent histone genes, which produce non-polyadenylated mRNAs. Here we show that DSIF and NELF contribute to the synthesis of small nuclear RNAs (snRNAs) through their association with Integrator, the large multisubunit complex responsible for 3' processing of pre-snRNAs. In HeLa cells, Pol II, Integrator, DSIF and NELF accumulate at the 3' end of the U1 snRNA gene. Knockdown of NELF results in misprocessing of U1, U2, U4 and U5 snRNAs, while DSIF is required for proper transcription of these genes. Knocking down NELF also disrupts transcription termination and induces the production of polyadenylated U1 transcripts caused by an enhanced recruitment of cleavage stimulation factor. Our results indicate that NELF plays a key role in determining the post-transcriptional fate of Pol II-transcribed genes.

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Section: Dsif and Nelf Interact With Integrator Via Spt5 And Nelf-asupporting

confidence: 89%

DSIF and NELF interact with Integrator to specify the correct post-transcriptional fate of snRNA genes

et al. 2014

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“…We did not detect RNA-dependent interactions between CBP and other eRNA interacting proteins, such as Mediator (Lai et al, 2013) or NELF (Schaukowitch et al, 2014) under native (Figure S2H) or PAR-CLIP (Figure S2I) conditions. Using published ChIPseq data (Kagey et al, 2010; Sun et al, 2011), we found no difference in Med-1 signal at CBP-RNAs compared to background RNAs (Figure S2J), although NELF signal was enriched at CBP-RNAs, suggesting active transcription at these regions (Figure S2J). Thus, we were unable to detect co-binding of CBP and other eRNA interacting proteins to the same RNAs.…”

Section: Resultsmentioning

confidence: 79%

RNA Binding to CBP Stimulates Histone Acetylation and Transcription

Bose

Donahue

Reinberg

et al. 2017

Cell

303

309

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Summary CBP/p300 are transcription co-activators whose binding is a signature of enhancers, cis-regulatory elements that control patterns of gene expression in multicellular organisms. Active enhancers produce bi-directional enhancer RNAs (eRNAs) and display CBP/p300 dependent histone acetylation. Here, we demonstrate that CBP binds directly to RNAs in vivo and in vitro. RNAs bound to CBP in vivo include a large number of eRNAs. Using steady-state histone acetyltransferase (HAT) assays we show that an RNA binding region in the HAT domain of CBP— a regulatory motif unique to CBP/p300—allows RNA to stimulate CBP’s HAT activity. At enhancers where CBP interacts with eRNAs, stimulation manifests in RNA-dependent changes in the histone acetylation mediated by CBP, such as H3K27ac, and by corresponding changes in gene expression. By interacting directly with CBP, eRNAs contribute to the unique chromatin structure at active enhancers, which in turn is required for regulation of target genes.

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“…CD4 ϩ T cells from peripheral blood of healthy donors were infected with NL4-3-luciferase (HIV-LUC) to generate an unbiased heterogeneous pool of HIV-infected primary T cells. Infected cells were transfected with siControl RNA or siRNA specific for NELF-B, which disrupts the NELF complex (31)(32)(33). Knockdowns were confirmed by immunoblot analyses and RT-PCR (Figs.…”

Section: Nelf Limits Hiv Transcription In Primary T Cells-ourmentioning

confidence: 99%

Negative Elongation Factor (NELF) Coordinates RNA Polymerase II Pausing, Premature Termination, and Chromatin Remodeling to Regulate HIV Transcription

Natarajan

Lester

Lee

et al. 2013

Journal of Biological Chemistry

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Background: Multiple mechanisms contribute to HIV latency, including NELF-mediated RNA polymerase II (RNAP II) pausing. Results: Paused RNAP II recruits a transcription termination factor and a transcriptional corepressor complex to the HIV promoter. Conclusion: Paused RNAP II couples premature transcription termination and chromatin remodeling to maintain HIV latency. Significance: Paused RNAP II may be targeted to purge latent HIV infection.

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Genetic and Genomic Analyses of RNA Polymerase II-pausing Factor in Regulation of Mammalian Transcription and Cell Growth

Cited by 25 publications

References 50 publications

DSIF and NELF interact with Integrator to specify the correct post-transcriptional fate of snRNA genes

DSIF and NELF interact with Integrator to specify the correct post-transcriptional fate of snRNA genes

RNA Binding to CBP Stimulates Histone Acetylation and Transcription

Negative Elongation Factor (NELF) Coordinates RNA Polymerase II Pausing, Premature Termination, and Chromatin Remodeling to Regulate HIV Transcription

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