Evidence map›Paper›PMID 42417395›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Dynamic Regulation of Endogenous Transcription Factor Hubs at Single-Molecule Resolution.

Shawn Yoshida, Yanghao Zhong, Akiko Kumagai, William G Dunphy, Shasha Chong

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Shawn YoshidaDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, USA.ORCID https://orcid.org/0000-0002-0866-2741
Yanghao ZhongDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, USA.ORCID https://orcid.org/0000-0002-0747-3041
Akiko KumagaiDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.ORCID https://orcid.org/0000-0003-2422-8053
William G DunphyDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.ORCID https://orcid.org/0000-0001-7598-8939
Shasha ChongDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, USA.

Funding

ENZYMOLOGY OF MITOSIS PROMOTING FACTOR (MPF)R01GM043974 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI DUNPHY, WILLIAM G · 1990 to 2022
$4.0M
Enzymology of Mitosis Promoting Factor (MPF)R37GM043974 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI DUNPHY, WILLIAM G · 2002 to 2011
$4.0M
Alex's Lemonade Stand Foundation Innovation Grant 1260879Edward Mallinckrodt, Jr. FoundationMerkin Institute for Translational ResearchNational Science Foundation Graduate Research Fellowship Program DGE-1745301NIGMS NIH HHS R01 GM043974NIGMS NIH HHS R37 GM043974NIH HHS GM043974Pew-Stewart Scholars Program for Cancer ResearchSearle Scholars ProgramThe Margaret E. Early Medical Research Trust
6 · The paper itself

Abstract

Eukaryotic transcription factors (TFs) form local, high-concentration hubs at specific genomic loci through dynamic, multivalent interactions mediated by their low-complexity domains, a behavior essential for transcriptional activation. Characterizing the dynamics and regulation of TF hubs requires high-resolution imaging of TFs in their native cellular environment; however, such biophysical characterization remains limited. Here, we combine CRISPR/Cas9-mediated genome editing and single-molecule microscopy to investigate the behaviors of endogenous oncogenic fusion TF EWS::FLI1 in Ewing sarcoma cells. EWS::FLI1 forms sub-diffraction-limit hubs with dissolution mechanisms that prevent macroscopic liquid-liquid phase separation. Hub formation is a neomorphic behavior of EWS::FLI1 not conferred by its parental proteins, EWSR1 and FLI1. During mitosis, EWS::FLI1 hubs dissolve, but EWS::FLI1 molecules continue to dynamically associate with mitotic chromosomes, consistent with a mitotic bookmarking role. Nascent RNA destabilizes EWS::FLI1 hubs without affecting their dimensions. Finally, LY2835219 and trabectedin, compounds previously reported to affect EWS::FLI1 function, disrupt and mislocalize endogenous EWS::FLI1 hubs, respectively, highlighting their therapeutic potential for treating Ewing sarcoma. Together, our results reveal new insights into the assembly and regulation of endogenous EWS::FLI1 hubs at an unprecedented resolution and establish a framework for biophysical and functional characterization of other TF hubs in the future.

Indexed as

Oncogene Proteins, FusionProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSSarcoma, EwingSingle Molecule ImagingTranscription FactorsCell Line, TumorHumansMitosisPhase SeparationEWS-FLI fusion proteinOncogene Proteins, FusionProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSTranscription FactorscondensatesEwing sarcomaEWS::FLI1phase separationsingle‐molecule microscopytranscriptional regulationtranscription factor hubs

Identifiers

PMID42417395
PMCPMC13343610

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.