Journal article Open Access

STAG2 mutations alter CTCF-anchored loop extrusion, reduce cis-regulatory interactions and EWSR1-FLI1 activity in Ewing sarcoma

Surdez, D.; Zaidi, S.; Grossetete, S.; Laud-Duval; Sole Ferre, A.; Mous, L.; Vourc'h, T.; Tirode, F.; Pierron, G.; Raynal, V.; Baulande, S.; Brunet, E.; Hill, V.; Delattre, O.


DataCite XML Export

<?xml version='1.0' encoding='utf-8'?>
<resource xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns="http://datacite.org/schema/kernel-4" xsi:schemaLocation="http://datacite.org/schema/kernel-4 http://schema.datacite.org/meta/kernel-4.1/metadata.xsd">
  <identifier identifierType="URL">https://zenodo.org/record/4748666</identifier>
  <creators>
    <creator>
      <creatorName>Surdez, D.</creatorName>
      <givenName>D.</givenName>
      <familyName>Surdez</familyName>
      <affiliation>INSERM U830, Équipe Labellisée LNCC, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Centre, Institut Curie Research Centre, 75005 Paris, France</affiliation>
    </creator>
    <creator>
      <creatorName>Zaidi, S.</creatorName>
      <givenName>S.</givenName>
      <familyName>Zaidi</familyName>
      <affiliation>INSERM U830, Équipe Labellisée LNCC, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Centre, Institut Curie Research Centre, 75005 Paris, France</affiliation>
    </creator>
    <creator>
      <creatorName>Grossetete, S.</creatorName>
      <givenName>S.</givenName>
      <familyName>Grossetete</familyName>
      <affiliation>INSERM U830, Équipe Labellisée LNCC, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Centre, Institut Curie Research Centre, 75005 Paris, France</affiliation>
    </creator>
    <creator>
      <creatorName>Laud-Duval</creatorName>
      <affiliation>INSERM U830, Équipe Labellisée LNCC, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Centre, Institut Curie Research Centre, 75005 Paris, France</affiliation>
    </creator>
    <creator>
      <creatorName>Sole Ferre, A.</creatorName>
      <givenName>A.</givenName>
      <familyName>Sole Ferre</familyName>
      <affiliation>INSERM UMR 1163, Laboratory of Genome Dynamics in the Immune System, Equipe Labellisée Ligue contre le Cancer and Université de Paris, Imagine Institute, 75005 Paris, France</affiliation>
    </creator>
    <creator>
      <creatorName>Mous, L.</creatorName>
      <givenName>L.</givenName>
      <familyName>Mous</familyName>
      <affiliation>INSERM U830, Équipe Labellisée LNCC, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Centre, Institut Curie Research Centre, 75005 Paris, France</affiliation>
    </creator>
    <creator>
      <creatorName>Vourc'h, T.</creatorName>
      <givenName>T.</givenName>
      <familyName>Vourc'h</familyName>
      <affiliation>UMR 168, Biology Inspired Physics at Mesoscales, PSL Research University, Institut Curie Research Centre, 75005 Paris, France</affiliation>
    </creator>
    <creator>
      <creatorName>Tirode, F.</creatorName>
      <givenName>F.</givenName>
      <familyName>Tirode</familyName>
      <affiliation>Univ Lyon, Université Claude Bernard Lyon 1, CNRS 5286, INSERM U1052, Cancer Research Center of Lyon, 69008 Lyon, France</affiliation>
    </creator>
    <creator>
      <creatorName>Pierron, G.</creatorName>
      <givenName>G.</givenName>
      <familyName>Pierron</familyName>
      <affiliation>Unité de Génétique Somatique, Service d'oncogénétique, Institut Curie, Centre Hospitalier, 75005 Paris, France</affiliation>
    </creator>
    <creator>
      <creatorName>Raynal, V.</creatorName>
      <givenName>V.</givenName>
      <familyName>Raynal</familyName>
      <affiliation>INSERM U830, Équipe Labellisée LNCC, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Centre, Institut Curie Research Centre, 75005 Paris, France</affiliation>
    </creator>
    <creator>
      <creatorName>Baulande, S.</creatorName>
      <givenName>S.</givenName>
      <familyName>Baulande</familyName>
      <affiliation>Institut Curie Genomics of Excellence (ICGex) Platform, PSL Université, Institut Curie Research Centre, 75005 Paris, France</affiliation>
    </creator>
    <creator>
      <creatorName>Brunet, E.</creatorName>
      <givenName>E.</givenName>
      <familyName>Brunet</familyName>
      <affiliation>INSERM UMR 1163, Laboratory of Genome Dynamics in the Immune System, Equipe Labellisée Ligue contre le Cancer and Université de Paris, Imagine Institute, 75005 Paris, France</affiliation>
    </creator>
    <creator>
      <creatorName>Hill, V.</creatorName>
      <givenName>V.</givenName>
      <familyName>Hill</familyName>
      <affiliation>INSERM U830, Équipe Labellisée LNCC, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Centre, Institut Curie Research Centre, 75005 Paris, France</affiliation>
    </creator>
    <creator>
      <creatorName>Delattre, O.</creatorName>
      <givenName>O.</givenName>
      <familyName>Delattre</familyName>
      <affiliation>INSERM U830, Équipe Labellisée LNCC, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Centre, Institut Curie Research Centre, 75005 Paris, France</affiliation>
    </creator>
  </creators>
  <titles>
    <title>STAG2 mutations alter CTCF-anchored loop extrusion, reduce cis-regulatory interactions and EWSR1-FLI1 activity in Ewing sarcoma</title>
  </titles>
  <publisher>Zenodo</publisher>
  <publicationYear>2021</publicationYear>
  <dates>
    <date dateType="Issued">2021-04-29</date>
  </dates>
  <language>en</language>
  <resourceType resourceTypeGeneral="JournalArticle"/>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://zenodo.org/record/4748666</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1016/j.ccell.2021.04.001</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://zenodo.org/communities/ipc</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="https://creativecommons.org/licenses/by/4.0/legalcode">Creative Commons Attribution 4.0 International</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">&lt;p&gt;STAG2, a cohesin family gene, is among the most recurrently mutated genes in cancer. STAG2 loss of function (LOF) is associated with aggressive behavior in Ewing sarcoma, a childhood cancer driven by aberrant transcription induced by the EWSR1-FLI1 fusion oncogene. Here, using isogenic Ewing cells, we show that, while STAG2 LOF profoundly changes the transcriptome, it does not significantly impact EWSR1-FLI1, CTCF/cohesin, or acetylated H3K27 DNA binding patterns. In contrast, it strongly alters the anchored dynamic loop extrusion process at boundary CTCF sites and dramatically decreases promoter-enhancer interactions, particularly affecting the expression of genes regulated by EWSR1-FLI1 at GGAA microsatellite neo-enhancers. Down-modulation of cis-mediated EWSR1-FLI1 activity, observed in STAG2-LOF conditions, is associated with enhanced migration and invasion properties of Ewing cells previously observed in EWSR1-FLI1low cells. Our study illuminates a process whereby STAG2-LOF fine-tunes the activity of an oncogenic transcription factor through altered CTCF-anchored loop extrusion and cis-mediated enhancer mechanisms.&lt;/p&gt;</description>
  </descriptions>
  <fundingReferences>
    <fundingReference>
      <funderName>European Commission</funderName>
      <funderIdentifier funderIdentifierType="Crossref Funder ID">10.13039/501100000780</funderIdentifier>
      <awardNumber awardURI="info:eu-repo/grantAgreement/EC/H2020/826121/">826121</awardNumber>
      <awardTitle>individualizedPaediatricCure: Cloud-based virtual-patient models for precision paediatric oncology</awardTitle>
    </fundingReference>
  </fundingReferences>
</resource>
38
156
views
downloads
Views 38
Downloads 156
Data volume 811.8 MB
Unique views 35
Unique downloads 147

Share

Cite as