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000168090 1001_ $$aKupp, Robert$$b0
000168090 245__ $$aZFTA-translocations constitute ependymoma chromatin remodeling and transcription factors.
000168090 260__ $$aPhiladelphia, Pa.$$c2021
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000168090 500__ $$a2021 Sep;11(9):2216-2229
000168090 520__ $$aZFTA (C11orf95)-a gene of unknown function-partners with a variety of transcriptional co-activators in translocations that drive supratentorial ependymoma, a frequently lethal brain tumor. Understanding the function of ZFTA is key to developing therapies that inhibit these fusion proteins. Here, using a combination of transcriptomics, chromatin immunoprecipitation-sequencing, and proteomics, we interrogated a series of deletion-mutant genes to identify a tri-partite transformation mechanism of ZFTA-containing fusions, including: spontaneous nuclear translocation, extensive chromatin binding, and SWI/SNF, SAGA and NuA4/Tip60 HAT chromatin modifier complex recruitment. Thereby, ZFTA tethers fusion proteins across the genome, modifying chromatin to an active state, and enabling its partner transcriptional co-activators to promote promiscuous expression of a transforming transcriptome. Using mouse models, we validate further those elements of ZFTA-fusion proteins that are critical for transformation-including ZFTA zinc fingers and partner gene transactivation domains-thereby unmasking vulnerabilities for therapeutic targeting.
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000168090 7001_ $$aRuff, Lisa$$b1
000168090 7001_ $$aTerranova, Sabrina$$b2
000168090 7001_ $$aNathan, Erica$$b3
000168090 7001_ $$00000-0002-8479-3110$$aBallereau, Stephane$$b4
000168090 7001_ $$00000-0002-1790-5469$$aStark, Rory$$b5
000168090 7001_ $$aSekhar Reddy Chilamakuri, Chandra$$b6
000168090 7001_ $$aHoffmann, Nadin$$b7
000168090 7001_ $$aWickham-Rahrmann, Katherine$$b8
000168090 7001_ $$aWiddess, Marcus$$b9
000168090 7001_ $$aArabzade, Amir$$b10
000168090 7001_ $$aZhao, Yanhua$$b11
000168090 7001_ $$00000-0002-2033-0758$$aVaradharajan, Srinidhi$$b12
000168090 7001_ $$0P:(DE-He78)1d5e6252296473fc060b71e61a22256c$$aZheng, Tuyu$$b13$$udkfz
000168090 7001_ $$aMurugesan, Mohankumar K$$b14
000168090 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b15$$udkfz
000168090 7001_ $$aKawauchi, Daisuke$$b16
000168090 7001_ $$0P:(DE-He78)a7c1bbac024fa232d9c6b78443328d9d$$aPajtler, Kristian W$$b17$$udkfz
000168090 7001_ $$aDeneen, Benjamin$$b18
000168090 7001_ $$00000-0001-9620-4742$$aMack, Stephen C$$b19
000168090 7001_ $$00000-0002-0809-668X$$aMasih, Katherine E$$b20
000168090 7001_ $$00000-0003-0130-2302$$aGryder, Berkley E$$b21
000168090 7001_ $$aKhan, Javed$$b22
000168090 7001_ $$00000-0001-7539-9472$$aGilbertson, Richard J$$b23
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000168090 9141_ $$y2021
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