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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 17, 2017 |
| Title |
Regulatory landscape fusion in rhabdomyosarcoma by interactions between the PAX3 promoter and FOXO1 regulatory elements |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Other
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| Summary |
Results: Using a combination of 4C-seq datasets, we were able to model the three-dimensional organisation of the translocated chromosome in a PAX3:FOXO1 fusion-positive alveolar rhabdomyosarcoma cell line. We show that PAX3 and FOXO1 regulatory landscapes fuse into a novel TAD, allowing the PAX3 promoter to interact ectopically with FOXO1 sequences with potential enhancer function. The borders of this novel TAD correspond to the original 5'- and 3'- borders of the PAX3 and FOXO1 TADs, respectively, suggesting that TAD organisation precedes the formation of regulatory long-range interactions.
Conclusions: Our results suggest that the chromosomal translocation that leads to ARMS development generates a novel TAD that favours ectopic PAX3:FOXO1 oncogene activation in non-PAX3 territories, which may be an essential step in the tumorigenic process, as expression in a particular cell type, the often elusive cell-of-origin, may be required for disease development.
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| Overall design |
4C-seq samples for FoxO1 and Pax3 gene promoters in E9.5 whole mouse embryos, as well as for the PAX3 promoter and several ECRs and CTCF binding sites present at the PAX3:FOXO1 locus in the patient-derived alveolar rhabdomyosarcoma (ARMS) cell line RMS.
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| Contributor(s) |
Vicente-GarcÃa C, Villarejo-Balcells B, Irastorza-Azcárate I, Naranjo S, Acemel RD, Tena JJ, Rigby PW, Devos DP, Gómez-Skarmeta JL, Carvajal JJ |
| Citation(s) |
28615069 |
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| Submission date |
Jun 01, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Juan J. Tena |
| E-mail(s) |
jjtenagu@upo.es
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| Organization name |
CABD/CSIC
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| Street address |
Univ. Pablo Olavide, Ctra. Utrera km1
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| City |
Sevilla |
| ZIP/Postal code |
41013 |
| Country |
Spain |
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| Platforms (3) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (11)
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| GSM1701245 |
4C-Seq for FoxO1 promoter in E9.5 mouse embryos |
| GSM1701246 |
4C-Seq for Pax3 promoter in E9.5 mouse embryos |
| GSM1701247 |
4C-Seq for PAX3 promoter in patient-derived RMS cells |
| GSM2435424 |
4C-Seq for viewpoint 1 (CTCF BS) in patient-derived RMS cells |
| GSM2435425 |
4C-Seq for viewpoint 2 (CTCF BS) in patient-derived RMS cells |
| GSM2435426 |
4C-Seq for viewpoint 4 (PAX3 enhancer) in patient-derived RMS cells |
| GSM2435427 |
4C-Seq for viewpoint 5 (FOXO1 ECR) in patient-derived RMS cells |
| GSM2435428 |
4C-Seq for viewpoint 6 (CTCF BS) in patient-derived RMS cells |
| GSM2435429 |
4C-Seq for viewpoint 7 (FOXO1 ECR) in patient-derived RMS cells |
| GSM2435430 |
4C-Seq for viewpoint 8 (CTCF BS) in patient-derived RMS cells |
| GSM2435431 |
4C-Seq for viewpoint 9 (CTCF BS) in patient-derived RMS cells |
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| Relations |
| BioProject |
PRJNA285501 |
| SRA |
SRP058950 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE69439_RAW.tar |
20.1 Mb |
(http)(custom) |
TAR (of BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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