Systematic multi-omics cell line profiling uncovers principles of Ewing sarcoma fusion oncogene-mediated gene regulation.
CP: Cancer
ChiP-seq
EWSR1-ERG
EWSR1-ETS
EWSR1-FLI1
Ewing sarcoma
enhancer
microsatellites
multi-omics
pediatric sarcoma
tumor heterogeneity
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
06 12 2022
06 12 2022
Historique:
received:
02
12
2021
revised:
25
08
2022
accepted:
08
11
2022
entrez:
8
12
2022
pubmed:
9
12
2022
medline:
15
12
2022
Statut:
ppublish
Résumé
Ewing sarcoma (EwS) is characterized by EWSR1-ETS fusion transcription factors converting polymorphic GGAA microsatellites (mSats) into potent neo-enhancers. Although the paucity of additional mutations makes EwS a genuine model to study principles of cooperation between dominant fusion oncogenes and neo-enhancers, this is impeded by the limited number of well-characterized models. Here we present the Ewing Sarcoma Cell Line Atlas (ESCLA), comprising whole-genome, DNA methylation, transcriptome, proteome, and chromatin immunoprecipitation sequencing (ChIP-seq) data of 18 cell lines with inducible EWSR1-ETS knockdown. The ESCLA shows hundreds of EWSR1-ETS-targets, the nature of EWSR1-ETS-preferred GGAA mSats, and putative indirect modes of EWSR1-ETS-mediated gene regulation, converging in the duality of a specific but plastic EwS signature. We identify heterogeneously regulated EWSR1-ETS-targets as potential prognostic EwS biomarkers. Our freely available ESCLA (http://r2platform.com/escla/) is a rich resource for EwS research and highlights the power of comprehensive datasets to unravel principles of heterogeneous gene regulation by chimeric transcription factors.
Identifiants
pubmed: 36476851
pii: S2211-1247(22)01644-8
doi: 10.1016/j.celrep.2022.111761
pmc: PMC10333306
mid: NIHMS1909974
pii:
doi:
Substances chimiques
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
111761Subventions
Organisme : NHGRI NIH HHS
ID : R01 HG010885
Pays : United States
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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