Evidence map›Paper›PMID 33446572›Full record

ArticleGenes & development2021

Acute perturbation strategies in interrogating RNA polymerase II elongation factor function in gene expression.

Bin Zheng, Yuki Aoi, Avani P Shah, Marta Iwanaszko, Siddhartha Das, Emily J Rendleman, Didi Zha, Nabiha Khan, Edwin R Smith, Ali Shilatifard

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 50 citations in OpenAlex.

  1. The CTNNB1-TRIM28 complex governs hormone-induced RNA polymerase II dynamics in kidney epithelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Structural basis for P-TEFb association with BRD4.bioRxiv : the preprint server for biology · 2026
    Article
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  19. Transcriptional elongation control of hypoxic response.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Bin ZhengSimpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Yuki AoiSimpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Avani P ShahSimpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Marta IwanaszkoSimpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Siddhartha DasSimpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Emily J RendlemanSimpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Didi ZhaSimpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Nabiha KhanSimpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Edwin R SmithSimpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Ali ShilatifardSimpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Northwestern University · US

Funding

Transcriptional Elongation Control in Development and DiseaseR01CA214035 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SHILATIFARD, ALI · 2016 to 2020
$3.0M
Histone Modification and Transcription Elongation in Human CancerR50CA211428 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SMITH, EDWIN R · 2016 to 2020
$925k
NCI NIH HHS R01 CA214035NCI NIH HHS R50 CA211428
6 · The paper itself

Abstract

The regulation of gene expression catalyzed by RNA polymerase II (Pol II) requires a host of accessory factors to ensure cell growth, differentiation, and survival under environmental stress. Here, using the auxin-inducible degradation (AID) system to study transcriptional activities of the bromodomain and extraterminal domain (BET) and super elongation complex (SEC) families, we found that the CDK9-containing BRD4 complex is required for the release of Pol II from promoter-proximal pausing for most genes, while the CDK9-containing SEC is required for activated transcription in the heat shock response. By using both the proteolysis targeting chimera (PROTAC) dBET6 and the AID system, we found that dBET6 treatment results in two major effects: increased pausing due to BRD4 loss, and reduced enhancer activity attributable to BRD2 loss. In the heat shock response, while auxin-mediated depletion of the AFF4 subunit of the SEC has a more severe defect than AFF1 depletion, simultaneous depletion of AFF1 and AFF4 leads to a stronger attenuation of the heat shock response, similar to treatment with the SEC inhibitor KL-1, suggesting a possible redundancy among SEC family members. This study highlights the usefulness of orthogonal acute depletion/inhibition strategies to identify distinct and redundant biological functions among Pol II elongation factor paralogs.

Indexed as

Bromodomain Containing ProteinsCell Cycle ProteinsCell Line, TumorGene ExpressionHCT116 CellsHeat-Shock ResponseHumansPeptide Elongation FactorsProteinsRNA Polymerase IITranscription FactorsBRD4 protein, humanbromodomain and extra-terminal domain protein, humanBromodomain Containing ProteinsCell Cycle ProteinsPeptide Elongation FactorsProteinsRNA Polymerase IITranscription Factorsauxin-inducible degradationBRD2BRD4enhancer activityheat shockPROTACsuper elongation complextranscription elongation

Identifiers

PMID33446572
PMCPMC7849361
OpenAlexW3125143977

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.