Epigenome editing of microsatellite repeats defines tumor-specific enhancer functions and dependencies.
Fiche du document
1 août 2018
- doi: 10.1101/gad.315192.118
- issn: 0890-9369
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1101/gad.315192.118
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/30042132
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1549-5477
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_491F4BB081459
info:eu-repo/semantics/openAccess , Copying allowed only for non-profit organizations , https://serval.unil.ch/disclaimer
Sujets proches
Speech--Transcription Language and languages--Transcription Transcribing TranscribingCiter ce document
G. Boulay et al., « Epigenome editing of microsatellite repeats defines tumor-specific enhancer functions and dependencies. », Serveur académique Lausannois, ID : 10.1101/gad.315192.118
Métriques
Partage / Export
Résumé
Various types of repetitive sequences are dysregulated in cancer. In Ewing sarcoma, the oncogenic fusion protein EWS-FLI1 induces chromatin features typical of active enhancers at GGAA microsatellite repeats, but the function of these sites has not been directly demonstrated. Here, by combining nascent transcription profiling with epigenome editing, we found that a subset of GGAA microsatellite repeats is transcriptionally active in Ewing sarcoma and that silencing individual repeats abolishes local nascent transcription and leads to markedly reduced expression of putative target genes. Epigenome silencing of these repeat sites does not affect gene expression in unrelated cells, can prevent the induction of gene expression by EWS-FLI1, and, in the case of a GGAA repeat that controls SOX2 expression from a distance of 470 kb, is sufficient to impair the growth of Ewing sarcoma xenografts. Using an experimental approach that is broadly applicable to testing different types of repetitive genomic elements, our study directly demonstrates that specific repeat microsatellites can have critical gene regulation functions in cancer and thus represent tumor-specific vulnerabilities that may be exploited to develop new therapies.