Journal Article

DKFZ-2021-00678

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png ZFTA-translocations constitute ependymoma chromatin remodeling and transcription factors.

Kupp, R. ; Ruff, L. ; Terranova, S. ; Nathan, E. ; Ballereau, S. ; Stark, R. ; Sekhar Reddy Chilamakuri, C. ; Hoffmann, N. ; Wickham-Rahrmann, K. ; Widdess, M. ; Arabzade, A. ; Zhao, Y. ; Varadharajan, S. ; Zheng, T.DKFZ* ; Murugesan, M. K. ; Pfister, S.DKFZ* ; Kawauchi, D. ; Pajtler, K. W.DKFZ* ; Deneen, B. ; Mack, S. C. ; Masih, K. E. ; Gryder, B. E. ; Khan, J. ; Gilbertson, R. J.

2021
Philadelphia, Pa.

This record in other databases:  

Please use a persistent id in citations: doi:10.1158/2159-8290.CD-20-1052

Abstract: ZFTA (C11orf95)-a gene of unknown function-partners with a variety of transcriptional co-activators in translocations that drive supratentorial ependymoma, a frequently lethal brain tumor. Understanding the function of ZFTA is key to developing therapies that inhibit these fusion proteins. Here, using a combination of transcriptomics, chromatin immunoprecipitation-sequencing, and proteomics, we interrogated a series of deletion-mutant genes to identify a tri-partite transformation mechanism of ZFTA-containing fusions, including: spontaneous nuclear translocation, extensive chromatin binding, and SWI/SNF, SAGA and NuA4/Tip60 HAT chromatin modifier complex recruitment. Thereby, ZFTA tethers fusion proteins across the genome, modifying chromatin to an active state, and enabling its partner transcriptional co-activators to promote promiscuous expression of a transforming transcriptome. Using mouse models, we validate further those elements of ZFTA-fusion proteins that are critical for transformation-including ZFTA zinc fingers and partner gene transactivation domains-thereby unmasking vulnerabilities for therapeutic targeting.

Note: 2021 Sep;11(9):2216-2229

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Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Essential Science Indicators ; IF >= 25 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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