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DOI | 10.1038/s41467-018-03833-5 |
TBX2 is a neuroblastoma core regulatory circuitry component enhancing MYCN/FOXM1 reactivation of DREAM targets | |
Decaesteker, Bieke1,2; Denecker, Geertrui1,2; Van Neste, Christophe1,2; Dolman, Emmy M.4; Van Loocke, Wouter1,2; Gartlgruber, Moritz5; Nunes, Carolina1,2; De Vloed, Fanny1,2; Depuydt, Pauline1,2; Verboom, Karen1,2; Rombaut, Dries1,2; Loontiens, Siebe1,2; De Wyn, Jolien1,2; Kholosy, Waleed M.4; Koopmans, Bianca4; Essing, Anke H. W.4; Herrmann, Carl6,7,8; Dreidax, Daniel5; Durinck, Kaat1,2; Deforce, Dieter2,9; Van Nieuwerburgh, Filip2,9; Henssen, Anton10,11,12; Versteeg, Rogier13; Boeva, Valentina3; Schleiermacher, Gudrun14; van Nes, Johan13; Mestdagh, Pieter1,2; Vanhauwaert, Suzanne1,2; Schulte, Johannes H.10; Westermann, Frank5; Molenaar, Jan J.4; De Preter, Katleen1,2; Speleman, Frank1,2 | |
2018-11-19 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | Belgium; France; Netherlands; Germany |
英文摘要 | Chromosome 17q gains are almost invariably present in high-risk neuroblastoma cases. Here, we perform an integrative epigenomics search for dosage-sensitive transcription factors on 17q marked by H3K27ac defined super-enhancers and identify TBX2 as top candidate gene. We show that TBX2 is a constituent of the recently established core regulatory circuitry in neuroblastoma with features of a cell identity transcription factor, driving proliferation through activation of p21-DREAM repressed FOXM1 target genes. Combined MYCN/TBX2 knockdown enforces cell growth arrest suggesting that TBX2 enhances MYCN sustained activation of FOXM1 targets. Targeting transcriptional addiction by combined CDK7 and BET bromodomain inhibition shows synergistic effects on cell viability with strong repressive effects on CRC gene expression and p53 pathway response as well as several genes implicated in transcriptional regulation. In conclusion, we provide insight into the role of the TBX2 CRC gene in transcriptional dependency of neuroblastoma cells warranting clinical trials using BET and CDK7 inhibitors. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000450405900014 |
WOS关键词 | SET ENRICHMENT ANALYSIS ; CHROMOSOME ARM 17Q ; TRANSCRIPTION FACTORS ; MYCN ; GENE ; EXPRESSION ; SCREEN ; GAIN ; HETEROGENEITY ; PROLIFERATION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203788 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium; 2.CRIG, B-9000 Ghent, Belgium; 3.Paris Descartes Univ, UMR S1016, Inst Cochin, INSERM U1016,CNRS UMR 8104, F-75014 Paris, France; 4.Princess Maxima Ctr Pediat Oncol, Dept Translat Res, NL-3584 Utrecht, Netherlands; 5.German Canc Res Ctr, Neuroblastoma Genom, D-69120 Heidelberg, Germany; 6.Heidelberg Univ, Inst Pharm & Mol Biotechnol, Neuenheimer Feld 267, D-69120 Heidelberg, Germany; 7.Heidelberg Univ, Bioquant Ctr, Neuenheimer Feld 267, D-69120 Heidelberg, Germany; 8.German Canc Res Ctr, Div Theoret Bioinformat, Neuenheimer Feld 280, D-69120 Heidelberg, Germany; 9.Univ Ghent, Lab Pharmaceut Biotechnol, B-9000 Ghent, Belgium; 10.Charite Univ Med Berlin, Dept Pediat Oncol & Hematol, D-13353 Berlin, Germany; 11.German Canc Consortium DKTK, D-69120 Heidelberg, Germany; 12.Berlin Inst Hlth, D-13353 Berlin, Germany; 13.Acad Med Ctr, Dept Oncogen, NL-1105 AZ Amsterdam, Netherlands; 14.PSL Res Univ, Inst Curie,SIREDO Care Innovat & Res Children Ado, Equipe Labellisee Ligue Canc,Dept Translat Res, Lab Rech Translat Oncol Pediat RTOP,Lab Gilles Th, F-75248 Paris, France |
推荐引用方式 GB/T 7714 | Decaesteker, Bieke,Denecker, Geertrui,Van Neste, Christophe,et al. TBX2 is a neuroblastoma core regulatory circuitry component enhancing MYCN/FOXM1 reactivation of DREAM targets[J]. NATURE COMMUNICATIONS,2018,9. |
APA | Decaesteker, Bieke.,Denecker, Geertrui.,Van Neste, Christophe.,Dolman, Emmy M..,Van Loocke, Wouter.,...&Speleman, Frank.(2018).TBX2 is a neuroblastoma core regulatory circuitry component enhancing MYCN/FOXM1 reactivation of DREAM targets.NATURE COMMUNICATIONS,9. |
MLA | Decaesteker, Bieke,et al."TBX2 is a neuroblastoma core regulatory circuitry component enhancing MYCN/FOXM1 reactivation of DREAM targets".NATURE COMMUNICATIONS 9(2018). |
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