publication . Article . 2021

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

Didier Surdez; Sakina Zaidi; Sandrine Grossetête; Karine Laud-Duval; Anna Sole Ferre; Lieke Mous; Thomas Vourc'h; Franck Tirode; Gaelle Pierron; Virginie Raynal; ...
Open Access English
  • Published: 29 Apr 2021
Abstract
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 ge...
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Subjects
Medical Subject Headings: fungi
free text keywords: Cell Biology, Cancer Research, Oncology
Funded by
EC| iPC
Project
iPC
individualizedPaediatricCure: Cloud-based virtual-patient models for precision paediatric oncology
  • Funder: European Commission (EC)
  • Project Code: 826121
  • Funding stream: H2020 | RIA
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Article . 2021
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Cancer Cell
Article . 2021
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