Evidence map›Paper›PMID 36124657›Full record

ArticleNucleic acids research2022

EWS/FLI mediated reprogramming of 3D chromatin promotes an altered transcriptional state in Ewing sarcoma.

Iftekhar A Showpnil, Julia Selich-Anderson, Cenny Taslim, Megann A Boone, Jesse C Crow, Emily R Theisen, Stephen L Lessnick

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

40 citing papers in PubMed, 51 citations in OpenAlex.

  1. Open-Label, Multicenter, Phase I/II, First-in-Human Trial of TK216: A First-Generation EWS::FLI1 Fusion Protein Antagonist in Ewing Sarcoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024
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  17. Liquid condensates: a new barrier to loop extrusion?Cellular and molecular life sciences : CMLS · 2025
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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

7 authors at 1 institution in 1 country.

Iftekhar A ShowpnilCenter for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.ORCID 0000-0002-3168-8114
Julia Selich-AndersonCenter for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
Cenny TaslimCenter for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
Megann A BooneCenter for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
Jesse C CrowCenter for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
Emily R TheisenCenter for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
Stephen L LessnickCenter for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
Nationwide Children's Hospital · US

Funding

Project 2: Evaluating the dynamic protein-protein interactions mediated by LCDs within EWS/FLI and its partners in living cells via single molecule imagingU54CA231641 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI LESSNICK, STEPHEN L. · 2018 to 2018
$6.2M
NCI NIH HHS U54 CA231641
6 · The paper itself

Abstract

Ewing sarcoma is a prototypical fusion transcription factor-associated pediatric cancer that expresses EWS/FLI or a highly related FET/ETS chimera. EWS/FLI dysregulates transcription to induce and maintain sarcomagenesis, but the mechanisms utilized are not fully understood. We therefore sought to define the global effects of EWS/FLI on chromatin conformation and transcription in Ewing sarcoma cells using a well-validated 'knock-down/rescue' model of EWS/FLI function in combination with next generation sequencing assays to evaluate how the chromatin landscape changes with loss, and recovery, of EWS/FLI expression. We found that EWS/FLI (and EWS/ERG) genomic localization is largely conserved across multiple patient-derived Ewing sarcoma cell lines. This EWS/FLI binding signature is associated with establishment of topologically-associated domain (TAD) boundaries, compartment activation, enhancer-promoter looping that involve both intra- and inter-TAD interactions, and gene activation. In addition, EWS/FLI co-localizes with the loop-extrusion factor cohesin to promote chromatin loops and TAD boundaries. Importantly, local chromatin features provide the basis for transcriptional heterogeneity in regulation of direct EWS/FLI target genes across different Ewing sarcoma cell lines. These data demonstrate a key role of EWS/FLI in mediating genome-wide changes in chromatin configuration and support the notion that fusion transcription factors serve as master regulators of three-dimensional reprogramming of chromatin.

Indexed as

Gene Expression Regulation, NeoplasticSarcoma, EwingCell Line, TumorChildChromatinHumansOncogene Proteins, FusionProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSChromatinEWS-FLI fusion proteinOncogene Proteins, FusionProto-Oncogene Protein c-fli-1RNA-Binding Protein EWS

Identifiers

PMID36124657
PMCPMC9508825
OpenAlexW4296778067

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.