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@ARTICLE{Kupp:168090,
author = {R. Kupp and L. Ruff and S. Terranova and E. Nathan and S.
Ballereau and R. Stark and C. Sekhar Reddy Chilamakuri and
N. Hoffmann and K. Wickham-Rahrmann and M. Widdess and A.
Arabzade and Y. Zhao and S. Varadharajan and T. Zheng$^*$
and M. K. Murugesan and S. Pfister$^*$ and D. Kawauchi and
K. W. Pajtler$^*$ and B. Deneen and S. C. Mack and K. E.
Masih and B. E. Gryder and J. Khan and R. J. Gilbertson},
title = {{ZFTA}-translocations constitute ependymoma chromatin
remodeling and transcription factors.},
journal = {Cancer discovery},
volume = {11},
number = {9},
issn = {2159-8290},
address = {Philadelphia, Pa.},
reportid = {DKFZ-2021-00678},
pages = {2216-2229},
year = {2021},
note = {2021 Sep;11(9):2216-2229},
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.},
cin = {B062 / HD01},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33741711},
doi = {10.1158/2159-8290.CD-20-1052},
url = {https://inrepo02.dkfz.de/record/168090},
}