Evidence map›Paper›PMID 40706597›Full record

ArticleMolecular cell2025

Single-molecule live imaging of subunit interactions and exchange within cellular regulatory complexes.

Thomas G W Graham, Claire Dugast-Darzacq, Gina M Dailey, Britney Weng, Sathvik Anantakrishnan, Xavier Darzacq, Robert Tjian

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Article
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  9. Small-molecule disruption of androgen receptor-dependent chromatin clusters.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  10. 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

7 authors.

Thomas G W GrahamDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: tgraha22@jh.edu.
Claire Dugast-DarzacqDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Gina M DaileyDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Britney WengDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Sathvik AnantakrishnanDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Xavier DarzacqDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: darzacq@berkeley.edu.
Robert TjianDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: tijcal@berkeley.edu.

Funding

Structure, Function, and Dynamics of Macro-molecular Complexes that Execute and Regulate Genome FunctionRM1GM139738 · NIGMS · CORNELL UNIVERSITY · PI Thomas George Wade Graham, Steven Zvi Josefowicz · 2021 to 2026
$14.4M
NIGMS NIH HHS RM1 GM139738
6 · The paper itself

Abstract

Cells are built from vast networks of interdependent molecular interactions. Here, we combine proximity-assisted photoactivation (PAPA) with automated fast single-molecule tracking (fSMT) to probe subunit interactions within endogenous protein complexes in live human cells. PAPA-fSMT revealed that the inactive positive transcription elongation factor b (P-TEFb):7SK ribonucleoprotein complex is predominantly mobile, not tethered to chromatin, and detected interaction of specific heterogeneous nuclear ribonucleoproteins (hnRNPs) with the 7SK complex. Cyclin-dependent kinase 9 (Cdk9) inhibition liberated hnRNP R from large RNAs, increased hnRNP R binding to 7SK, and evicted P-TEFb from 7SK within minutes-consistent with rapid, homeostatic negative feedback regulation of P-TEFb by competing protein-RNA interactions. Association with the coactivator BRD4 increased P-TEFb chromatin binding, which depended on the BRD4 bromodomains. Finally, PAPA detected the release of P-TEFb from 7SK by the HIV transcriptional activator Tat. Our results illuminate aspects of P-TEFb regulation that were previously inaccessible in live cells and open a route to probe subunit interactions and exchange within endogenous regulatory complexes.

Indexed as

Positive Transcriptional Elongation Factor BSingle Molecule ImagingBromodomain Containing ProteinsCell Cycle ProteinsChromatinCyclin-Dependent Kinase 9HEK293 CellsHeLa CellsHumansNuclear ProteinsProtein BindingTranscription FactorsBRD4 protein, humanBromodomain Containing ProteinsCDK9 protein, humanCell Cycle ProteinsChromatinCyclin-Dependent Kinase 9Nuclear ProteinsPositive Transcriptional Elongation Factor BTranscription Factors7SK complexBRD4fast single-molecule trackingfSMTheterogeneous nuclear ribonucleoproteinsHIV TathnRNP RhnRNPsPAPApositive transcription elongation factor bprotein-protein interactionsproximity-assisted photoactivationP-TEFbtranscriptional regulation

Identifiers

PMID40706597
PMCPMC12327956

What Socratic holds

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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 Socratic graph.