183:
The core motif of ETS transcription factors includes a GGAA sequence. EWS/FLI1 may bind to such sequences with greater affinity than the wild-type ETS member disrupting the normal regulation of ETS target
176:
of FLI1. While wild-type FLI1 recognizes an ACCGGAAG core sequence, EWS/FLI1 preferentially binds GGAA-repetitive regions. There is a positive correlation between the number of consecutive GGAA
98:
mutant tumors. Chromoplectic looping appears to be the mechanism involved in forming the EWS/ERG variant transcription factor. This preference is probably due to
296:"Detection of the (11;22)(q24;q12) translocation of Ewing's sarcoma and peripheral neuroectodermal tumor by reverse transcription polymerase chain reaction"
335:
Zucman, Jessica (November 1992). "Cloning and characterization of the Ewing's sarcoma and peripheral neuroepithelioma t(11;22) translocation breakpoints".
61:
709:"EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma"
69:
650:"Identification of two types of GGAA-microsatellites and their roles in EWS/FLI binding and gene regulation in Ewing sarcoma"
106:
being in opposite orientations on the genome precluding the production of functional EWS/ERG via a reciprocal translocation.
380:"Functional genomic screening reveals splicing of the EWS-FLI1 fusion transcript as a vulnerability in Ewing sarcoma"
247:"Genomic landscape of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations"
76:
41:
with the remaining 10% of fusions substituting one fusion partner with a closely related family member (e.g.
478:"EWS-FLI-1 Expression Triggers a Ewing's Sarcoma Initiation Program in Primary Human Mesenchymal Stem Cells"
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It has recently been appreciated that almost half of EWS and FLI1 fusions are a result of
665:
609:"The FLI-1 and Chimeric EWS-FLI-1Oncoproteins Display Similar DNA Binding Specificities"
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429:"Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors"
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568:"Oncogenic EWS-Fli1 interacts with hsRPB7, a subunit of human RNA polymerase II"
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state. EWS/FLI1 accomplishes this through a set of complementary mechanisms:
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Most fusions between EWS and FLI1 result from a t(11;22)(q24;q12) reciprocal
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72:, Friend leukemia integration 1 transcription factor (abbreviated FLI1).
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EWS/FLI1 functions as both a pioneering transcription factor and potent
143:
26:
519:"Cancer-Specific Retargeting of BAF Complexes by a Prion-like Domain"
60:
is a gene on chromosome 22 whose mRNA is translated into the protein
80:
38:
46:
79:. This translocation creates a chimeric transcript which fuses
95:
83:
1-7 of EWSR1 to exons 6-9 (or less commonly 5-9) of FLI1.
118:. Its expression leads to a complete restructuring of the
68:
resides on chromosome 11 where it encodes a member of the
90:. Evidence of chromoplectic looping is enriched in both
37:. It is found in approximately 90% of all Ewing sarcoma
202:Grünewald, TGP (July 5, 2018). "Ewing sarcoma".
180:, EWS/FLI1 binding, and target gene expression.
8:
138:of EWSR1. This allows EWS/FLI1 to both bind
427:Anderson, Nathaniel D (February 28, 2019).
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648:Johnson, Kirsten (November 1, 2017).
7:
517:Boulay, Gaylor (21 September 2017).
378:Grohar, Patrick (January 26, 2016).
613:The Journal of Biological Chemistry
566:Petermann, Robert (6 August 1998).
134:of EWS/FLI1 retains the prion-like
707:Riggi, Nicolò (October 30, 2014).
476:Riggi, Nicolò Riggi (April 2008).
14:
300:The American Journal of Pathology
122:of the cell of origin to favor a
62:Ewing sarcoma breakpoint region 1
294:Downing, J. R. (November 1993).
337:Genes, Chromosomes & Cancer
70:ETS transcription factor family
245:Tirode, Franck (May 1, 2015).
204:Nature Reviews Disease Primers
1:
626:10.1016/S0021-9258(17)32437-7
607:Mao, Xiaohong (8 July 1998).
495:10.1158/0008-5472.CAN-07-1761
675:10.1371/journal.pone.0186275
396:10.1016/j.celrep.2015.12.063
263:10.1158/2159-8290.CD-14-0622
146:. These interactions change
64:(abbreviated EWS). The gene
725:10.1016/j.ccell.2014.10.004
789:
535:10.1016/j.cell.2017.07.036
216:10.1038/s41572-018-0003-x
172:of EWS/FLI1 retains the
77:chromosome translocation
445:10.1126/science.aam8419
158:effectively generating
585:10.1038/sj.onc.1201964
349:10.1002/gcc.2870050402
136:transactivation domain
666:2017PLoSO..1286275J
619:(27): 18216–18222.
439:(6405): eaam8419.
174:DNA-binding domain
257:(11): 1342–1353.
156:DNA-binding sites
140:RNA polymerase II
110:Molecular Biology
16:Oncogenic protein
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719:(5): 668–681.
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35:Ewing sarcoma
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31:pathognomonic
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154:at EWS/FLI1
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19:
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713:Cancer Cell
152:euchromatin
144:BAF complex
124:tumorigenic
88:chromoplexy
757:Categories
189:References
170:C-terminus
132:N-terminus
92:metastatic
163:enhancers
24:oncogenic
763:Proteins
743:25453903
694:29091716
654:PLOS ONE
572:Oncogene
553:28844694
504:18381423
463:30166462
414:26776507
365:23718350
281:25223734
232:49571421
224:29977059
210:(5): 5.
116:oncogene
29:that is
20:EWS/FLI1
768:Sarcoma
734:4492343
685:5665490
662:Bibcode
635:7517940
594:9704926
544:6791823
454:6176908
433:Science
405:4755295
357:1283315
322:8238248
313:1887175
272:4264969
160:de novo
27:protein
773:Cancer
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184:genes.
53:Origin
39:tumors
22:is an
361:S2CID
228:S2CID
100:EWSR1
81:exons
58:EWSR1
739:PMID
690:PMID
631:PMID
590:PMID
549:PMID
523:Cell
500:PMID
459:PMID
410:PMID
353:PMID
318:PMID
277:PMID
220:PMID
168:The
130:The
102:and
94:and
66:FLI1
47:FLI1
45:for
33:for
729:PMC
721:doi
680:PMC
670:doi
621:doi
617:269
580:doi
539:PMC
531:doi
527:171
490:doi
449:PMC
441:doi
437:361
400:PMC
392:doi
345:doi
308:PMC
304:143
267:PMC
259:doi
212:doi
150:to
104:ERG
96:p53
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43:ERG
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