Evidence map›Paper›PMID 39121214›Full record

ArticleScience advances2024

3D chromatin architecture, BRD4, and Mediator have distinct roles in regulating genome-wide transcriptional bursting and gene network.

Pawel Trzaskoma, SeolKyoung Jung, Aleksandra Pękowska, Christopher H Bohrer, Xiang Wang, Faiza Naz, Stefania Dell'Orso, Wendy D Dubois, Ana Olivera, Supriya V Vartak and 9 more

Abstract read
In one paragraph

Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing 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

22 citing papers in PubMed.

  1. The molecular basis of transcription initiation by RNA polymerase II.Nature reviews. Molecular cell biology · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Invariant nonequilibrium dynamics in gene regulation optimize information flow.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. What makes genes burst.Trends in cell biology · 2026
    Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article
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

19 authors.

Pawel TrzaskomaNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-5823-6572
SeolKyoung JungNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0009-0004-7679-5919
Aleksandra PękowskaNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-0425-4388
Christopher H BohrerNational Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-2017-7933
Xiang WangNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-7190-9233
Faiza NazNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Stefania Dell'OrsoNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-1634-5631
Wendy D DuboisNational Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-8664-7715
Ana OliveraNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Supriya V VartakNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Yongbing ZhaoNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Subhashree NayakNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-7088-9461
Andrew OvermillerNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-3169-0556
Maria I MorassoNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-9632-9593
Vittorio SartorelliNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-9284-3675
Daniel R LarsonNational Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-9253-3055
Carson C ChowNational Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-1463-9553
Rafael CasellasNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-2981-4959
John J O'SheaNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-6456-9752

Funding

Stat transcription factors in immunoregulation and autoimmune diseaseZIAAR041159 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI O'SHEA, JOHN · 2009 to 2025
$49.3M
RAG and AID biologyZIAAR041148 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI O'SHEA, JOHN · 2009 to 2025
$44.8M
Control of Myogenesis and Regulation of MyoD Post-Transcriptional ModificationsZIAAR041126 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI SARTORELLI, VITTORIO · 2009 to 2025
$28.7M
Regulation Of Epidermal DifferentiationZIAAR041124 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI MORASSO, MARIA · 2009 to 2024
$21.1M
Modeling gene transcriptionZIADK075069 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI CHOW, CARSON · 2012 to 2025
$2.9M
6 · The paper itself

Abstract

Discontinuous transcription is evolutionarily conserved and a fundamental feature of gene regulation; yet, the exact mechanisms underlying transcriptional bursting are unresolved. Analyses of bursting transcriptome-wide have focused on the role of cis-regulatory elements, but other factors that regulate this process remain elusive. We applied mathematical modeling to single-cell RNA sequencing data to infer bursting dynamics transcriptome-wide under multiple conditions to identify possible molecular mechanisms. We found that Mediator complex subunit 26 (MED26) primarily regulates frequency, MYC regulates burst size, while cohesin and Bromodomain-containing protein 4 (BRD4) can modulate both. Despite comparable effects on RNA levels among these perturbations, acute depletion of MED26 had the most profound impact on the entire gene regulatory network, acting downstream of chromatin spatial architecture and without affecting TATA box-binding protein (TBP) recruitment. These results indicate that later steps in the initiation of transcriptional bursts are primary nodes for integrating gene networks in single cells.

Indexed as

Cell Cycle ProteinsChromatinGene Regulatory NetworksTranscription FactorsTranscription, GeneticBromodomain Containing ProteinsCohesinsGene Expression RegulationHumansMediator ComplexSingle-Cell AnalysisTranscriptomeBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsChromatinCohesinsMediator ComplexTranscription Factors

Identifiers

PMID39121214
PMCPMC11313860

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Registered trials

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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.