Evidence map›Paper›PMID 38102136›Full record

ArticleNature communications2023

PAX3-FOXO1 uses its activation domain to recruit CBP/P300 and shape RNA Pol2 cluster distribution.

Yaw Asante, Katharina Benischke, Issra Osman, Quy A Ngo, Jakob Wurth, Dominik Laubscher, Hyunmin Kim, Bhavatharini Udhayakumar, Md Imdadul H Khan, Diana H Chin and 11 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
4.0field-weighted citation impact, top 6% of its field
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

26 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
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  9. BAF complex-independent gene activation by SS18::SSX.bioRxiv : the preprint server for biology · 2026
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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

21 authors at 4 institutions in 3 countries.

Yaw Asante *Department of Nutrition, Case Western Reserve University, Cleveland, OH, USA.ORCID 0000-0002-6924-8632
Katharina Benischke *University Children's Hospital, Children's Research Center and Department of Oncology, Steinwiesstrasse 75, CH-8032, Zürich, Switzerland.
Issra Osman *Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.ORCID 0000-0001-5918-4543
Quy A NgoUniversity Children's Hospital, Children's Research Center and Department of Oncology, Steinwiesstrasse 75, CH-8032, Zürich, Switzerland.
Jakob WurthUniversity Children's Hospital, Children's Research Center and Department of Oncology, Steinwiesstrasse 75, CH-8032, Zürich, Switzerland.ORCID 0000-0002-1328-7122
Dominik LaubscherUniversity Children's Hospital, Children's Research Center and Department of Oncology, Steinwiesstrasse 75, CH-8032, Zürich, Switzerland.
Hyunmin KimDepartment of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.ORCID 0000-0003-0835-5044
Bhavatharini UdhayakumarDepartment of Nutrition, Case Western Reserve University, Cleveland, OH, USA.
Md Imdadul H KhanDepartment of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.ORCID 0000-0001-8002-5600
Diana H ChinDepartment of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.ORCID 0000-0002-1645-3552
Jadon PorchDepartment of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.
Maharshi ChakrabortyAxiotl Inc, Cleveland, OH, USA.
Richard SallariAxiotl Inc, Cleveland, OH, USA.
Olivier DelattreINSERM U830, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Center, Institut Curie Research Center, Paris, France.ORCID 0000-0002-8730-2276
Sakina ZaidiINSERM U830, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Center, Institut Curie Research Center, Paris, France.ORCID 0000-0001-9128-0287
Sarah MoriceBalgrist University Hospital, Faculty of Medicine, University of Zurich (UZH), Zurich, Switzerland.
Didier SurdezBalgrist University Hospital, Faculty of Medicine, University of Zurich (UZH), Zurich, Switzerland.ORCID 0000-0002-7118-7859
Sara G DanielliUniversity Children's Hospital, Children's Research Center and Department of Oncology, Steinwiesstrasse 75, CH-8032, Zürich, Switzerland.
Beat W SchäferUniversity Children's Hospital, Children's Research Center and Department of Oncology, Steinwiesstrasse 75, CH-8032, Zürich, Switzerland. beat.schaefer@kispi.uzh.ch.ORCID 0000-0001-5988-2915
Berkley E GryderDepartment of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA. berkley.gryder@case.edu.ORCID 0000-0003-0130-2302
Marco WachtelUniversity Children's Hospital, Children's Research Center and Department of Oncology, Steinwiesstrasse 75, CH-8032, Zürich, Switzerland. marco.wachtel@kispi.uzh.ch.ORCID 0000-0002-6077-3692
Case Western Reserve University · USUniversity Children's Hospital Zurich · CHInserm · FRUniversity of Zurich · CH

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
NIGMS NIH HHS T32 GM007250
6 · The paper itself

Abstract

Activation of oncogenic gene expression from long-range enhancers is initiated by the assembly of DNA-binding transcription factors (TF), leading to recruitment of co-activators such as CBP/p300 to modify the local genomic context and facilitate RNA-Polymerase 2 (Pol2) binding. Yet, most TF-to-coactivator recruitment relationships remain unmapped. Here, studying the oncogenic fusion TF PAX3-FOXO1 (P3F) from alveolar rhabdomyosarcoma (aRMS), we show that a single cysteine in the activation domain (AD) of P3F is important for a small alpha helical coil that recruits CBP/p300 to chromatin. P3F driven transcription requires both this single cysteine and CBP/p300. Mutants of the cysteine reduce aRMS cell proliferation and induce cellular differentiation. Furthermore, we discover a profound dependence on CBP/p300 for clustering of Pol2 loops that connect P3F to its target genes. In the absence of CBP/p300, Pol2 long range enhancer loops collapse, Pol2 accumulates in CpG islands and fails to exit the gene body. These results reveal a potential novel axis for therapeutic interference with P3F in aRMS and clarify the molecular relationship of P3F and CBP/p300 in sustaining active Pol2 clusters essential for oncogenic transcription.

Indexed as

Rhabdomyosarcoma, AlveolarRNA Polymerase IICysteineForkhead Box Protein O1HumansPAX3 Transcription FactorProtein BindingRNATranscriptional ActivationTranscription FactorsCysteineForkhead Box Protein O1FOXO1 protein, humanPAX3 protein, humanPAX3 Transcription FactorRNARNA Polymerase IITranscription Factors

Identifiers

PMID38102136
PMCPMC10724205
OpenAlexW4389815087

What Socratic 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 Socratic graph.