Epigenome Mapping Reveals Distinct Modes of Gene Regulation and Widespread Enhancer Reprogramming by the Oncogenic Fusion Protein EWS-FLI1

Cell Reports

Volumn 10, Issue 7, 2015, Pages 1082-1095

  Tomazou, Eleni M ^a   Sheffield, Nathan C ^b   Schmidl, Christian ^b   Schuster, Michael ^b   Schönegger, Andreas ^b   Datlinger, Paul ^b   Kubicek, Stefan ^b   Bock, Christoph ^b,c,d   Kovar, Heinrich ^a,c  

^a CHILDREN'S CANCER RESEARCH INSTITUTE   (Austria)

^b ERICH SCHMID INSTITUTE OF MATERIALS SCIENCE   (Austria)

^c MEDICAL UNIVERSITY OF VIENNA   (Austria)

^d MAX PLANCK INSTITUTE FOR INFORMATICS   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; ENTINOSTAT; EWS-FLI1 PROTEIN; HISTONE; HISTONE DEACETYLASE INHIBITOR; HYBRID PROTEIN; ONCOGENIC FUSION PROTEIN; RNA BINDING PROTEIN; ROMIDEPSIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR AP 1; TRANSCRIPTION FACTOR E2F; TRANSCRIPTOME; UNCLASSIFIED DRUG; VORINOSTAT; CHROMATIN; EWS-FLI FUSION PROTEIN; HISTONE DEACETYLASE; ONCOPROTEIN; RNA BINDING PROTEIN EWS; SMALL INTERFERING RNA; TRANSCRIPTION FACTOR FLI 1;

ARTICLE; CHROMATIN; CHROMOSOME TRANSLOCATION; DNA METHYLATION; DOWN REGULATION; ENHANCER REGION; EPIGENETICS; EWING SARCOMA; GENE CONTROL; GENE MAPPING; GENETIC ASSOCIATION; HISTONE ACETYLATION; HUMAN; HUMAN CELL; ONCOGENE; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; TRANSCRIPTION REGULATION; ACETYLATION; CHEMISTRY; CHROMOSOME MAP; CLUSTER ANALYSIS; DRUG EFFECTS; GENETIC EPIGENESIS; GENETICS; METABOLISM; NUCLEAR REPROGRAMMING; PATHOLOGY; PROMOTER REGION; TUMOR CELL LINE;

ACETYLATION; CELL LINE, TUMOR; CELLULAR REPROGRAMMING; CHROMATIN; CHROMOSOME MAPPING; CLUSTER ANALYSIS; DNA METHYLATION; DOWN-REGULATION; E2F TRANSCRIPTION FACTORS; EPIGENESIS, GENETIC; HISTONE DEACETYLASE INHIBITORS; HISTONE DEACETYLASES; HISTONES; HUMANS; ONCOGENE PROTEINS, FUSION; PROMOTER REGIONS, GENETIC; PROTO-ONCOGENE PROTEIN C-FLI-1; RNA, SMALL INTERFERING; RNA-BINDING PROTEIN EWS; SARCOMA, EWING; TRANSCRIPTION FACTOR AP-1; TRANSCRIPTOME;

EID: 84924614665     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2015.01.042     Document Type: Article

References (36)

1. Arnaldez F.I., Helman L.J. New strategies in ewing sarcoma: lost in translation?. Clin. Cancer Res. 2014, 20:3050-3056.
2. Bailly R.A., Bosselut R., Zucman J., Cormier F., Delattre O., Roussel M., Thomas G., Ghysdael J. DNA-binding and transcriptional activation properties of the EWS-FLI-1 fusion protein resulting from the t(11;22) translocation in Ewing sarcoma. Mol. Cell. Biol. 1994, 14:3230-3241.
3. Bernstein M., Kovar H., Paulussen M., Randall R.L., Schuck A., Teot L.A., Juergens H. Ewing's sarcoma family of tumors: current management. Oncologist 2006, 11:503-519.
4. Bernstein B.E., Birney E., Dunham I., Green E.D., Gunter C., Snyder M. An integrated encyclopedia of DNA elements in the human genome. Nature 2012, 489:57-74. ENCODE Project Consortium.
5. Bilke S., Schwentner R., Yang F., Kauer M., Jug G., Walker R.L., Davis S., Zhu Y.J., Pineda M., Meltzer P.S., Kovar H. Oncogenic ETS fusions deregulate E2F3 target genes in Ewing sarcoma and prostate cancer. Genome Res. 2013, 23:1797-1809.
6. Brohl A.S., Solomon D.A., Chang W., Wang J., Song Y., Sindiri S., Patidar R., Hurd L., Chen L., Shern J.F., et al. The genomic landscape of the Ewing Sarcoma family of tumors reveals recurrent STAG2 mutation. PLoS Genet. 2014, 10:e1004475.
7. Buenrostro J.D., Giresi P.G., Zaba L.C., Chang H.Y., Greenleaf W.J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 2013, 10:1213-1218.
8. Carrillo J., García-Aragoncillo E., Azorín D., Agra N., Sastre A., González-Mediero I., García-Miguel P., Pestaña A., Gallego S., Segura D., Alonso J. Cholecystokinin down-regulation by RNA interference impairs Ewing tumor growth. Clin. Cancer Res. 2007, 13:2429-2440.
9. Chen J., Odenike O., Rowley J.D. Leukaemogenesis: more than mutant genes. Nat. Rev. Cancer 2010, 10:23-36.
10. Creyghton M.P., Cheng A.W., Welstead G.G., Kooistra T., Carey B.W., Steine E.J., Hanna J., Lodato M.A., Frampton G.M., Sharp P.A., et al. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc. Natl. Acad. Sci. USA 2010, 107:21931-21936.
11. Crompton B.D., Stewart C., Taylor-Weiner A., Alexe G., Kurek K.C., Calicchio M.L., Kiezun A., Carter S.L., Shukla S.A., Mehta S.S., et al. The genomic landscape of pediatric Ewing sarcoma. Cancer Discov. 2014, 4:1326-1341.
12. Delattre O., Zucman J., Melot T., Garau X.S., Zucker J.M., Lenoir G.M., Ambros P.F., Sheer D., Turc-Carel C., Triche T.J., et al. The Ewing family of tumors-a subgroup of small-round-cell tumors defined by specific chimeric transcripts. N.Engl. J. Med. 1994, 331:294-299.
13. An integrated encyclopedia of DNA elements in the human genome. Nature 2012, 489:57-74. ENCODE Project Consortium.
14. Hahm K.B., Cho K., Lee C., Im Y.H., Chang J., Choi S.G., Sorensen P.H., Thiele C.J., Kim S.J. Repression of the gene encoding the TGF-beta type II receptor is a major target of the EWS-FLI1 oncoprotein. Nat. Genet. 1999, 23:222-227.
15. Hnisz D., Abraham B.J., Lee T.I., Lau A., Saint-André V., Sigova A.A., Hoke H.A., Young R.A. Super-enhancers in the control of cell identity and disease. Cell 2013, 155:934-947.
16. Huether R., Dong L., Chen X., Wu G., Parker M., Wei L., Ma J., Edmonson M.N., Hedlund E.K., Rusch M.C., et al. The landscape of somatic mutations in epigenetic regulators across 1,000 paediatric cancer genomes. Nat. Commun. 2014, 5:3630.
17. Kauer M., Ban J., Kofler R., Walker B., Davis S., Meltzer P., Kovar H. A molecular function map of Ewing's sarcoma. PLoS ONE 2009, 4:e5415.
18. Kovar H. Downstream EWS/FLI1 - upstream Ewing's sarcoma. Genome Med. 2010, 2:8.
19. Lawrence M.S., Stojanov P., Polak P., Kryukov G.V., Cibulskis K., Sivachenko A., Carter S.L., Stewart C., Mermel C.H., Roberts S.A., et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 2013, 499:214-218.
20. Lovén J., Hoke H.A., Lin C.Y., Lau A., Orlando D.A., Vakoc C.R., Bradner J.E., Lee T.I., Young R.A. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell 2013, 153:320-334.
21. Macconaill L.E., Garraway L.A. Clinical implications of the cancer genome. J.Clin. Oncol. 2010, 28:5219-5228.
22. Mitelman F., Johansson B., Mertens F. Fusion genes and rearranged genes as a linear function of chromosome aberrations in cancer. Nat. Genet. 2004, 36:331-334.
23. Ohno T., Rao V.N., Reddy E.S. EWS/Fli-1 chimeric protein is a transcriptional activator. Cancer Res. 1993, 53:5859-5863.
24. Prieur A., Tirode F., Cohen P., Delattre O. EWS/FLI-1 silencing and gene profiling of Ewing cells reveal downstream oncogenic pathways and a crucial role for repression of insulin-like growth factor binding protein 3. Mol. Cell. Biol. 2004, 24:7275-7283.
25. Rada-Iglesias A., Bajpai R., Swigut T., Brugmann S.A., Flynn R.A., Wysocka J. A unique chromatin signature uncovers early developmental enhancers in humans. Nature 2011, 470:279-283.
26. Riggi N., Suvà M.L., Suvà D., Cironi L., Provero P., Tercier S., Joseph J.M., Stehle J.C., Baumer K., Kindler V., Stamenkovic I. EWS-FLI-1 expression triggers a Ewing's sarcoma initiation program in primary human mesenchymal stem cells. Cancer Res. 2008, 68:2176-2185.
27. Riggi N., Knoechel B., Gillespie S.M., Rheinbay E., Boulay G., Suvà M.L., Rossetti N.E., Boonseng W.E., Oksuz O., Cook E.B., et al. EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma. Cancer Cell 2014, 26:668-681.
28. Rivera C.M., Ren B. Mapping human epigenomes. Cell 2013, 155:39-55.
29. Sanchez G., Bittencourt D., Laud K., Barbier J., Delattre O., Auboeuf D., Dutertre M. Alteration of cyclin D1 transcript elongation by a mutated transcription factor up-regulates the oncogenic D1b splice isoform in cancer. Proc. Natl. Acad. Sci. USA 2008, 105:6004-6009.
30. Sankar S., Bell R., Stephens B., Zhuo R., Sharma S., Bearss D.J., Lessnick S.L. Mechanism and relevance of EWS/FLI-mediated transcriptional repression in Ewing sarcoma. Oncogene 2013, 32:5089-5100.
31. Sheffield N.C., Thurman R.E., Song L., Safi A., Stamatoyannopoulos J.A., Lenhard B., Crawford G.E., Furey T.S. Patterns of regulatory activity across diverse human cell types predict tissue identity, transcription factor binding, and long-range interactions. Genome Res. 2013, 23:777-788.
32. Smith R., Owen L.A., Trem D.J., Wong J.S., Whangbo J.S., Golub T.R., Lessnick S.L. Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma. Cancer Cell 2006, 9:405-416.
33. Stadler M.B., Murr R., Burger L., Ivanek R., Lienert F., Schöler A., van Nimwegen E., Wirbelauer C., Oakeley E.J., Gaidatzis D., et al. DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature 2011, 480:490-495.
34. Tirode F., Laud-Duval K., Prieur A., Delorme B., Charbord P., Delattre O. Mesenchymal stem cell features of Ewing tumors. Cancer Cell 2007, 11:421-429.
35. Tirode F., Surdez D., Ma X., Parker M., Le Deley M.C., Bahrami A., Zhang Z., Lapouble E., Grossetête-Lalami S., Rusch M., et al. Genomic landscape of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations. Cancer Discov. 2014, 4:1342-1353. St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project and the International Cancer Genome Consortium.
36. Whyte W.A., Orlando D.A., Hnisz D., Abraham B.J., Lin C.Y., Kagey M.H., Rahl P.B., Lee T.I., Young R.A. Master transcription factors andmediator establish super-enhancers at key cell identity genes. Cell 2013, 153:307-319.