Dataset Information


Regulatory landscape fusion in rhabdomyosarcoma by interactions between the PAX3 promoter and FOXO1 regulatory elements

ABSTRACT: 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. 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.

INSTRUMENT(S): Illumina HiSeq 2000 (Homo sapiens)

SUBMITTER: Juan J. Tena  

PROVIDER: GSE69439 | GEO | 2017-04-17



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Regulatory landscape fusion in rhabdomyosarcoma through interactions between the PAX3 promoter and FOXO1 regulatory elements.

Vicente-García Cristina C   Villarejo-Balcells Barbara B   Irastorza-Azcárate Ibai I   Naranjo Silvia S   Acemel Rafael D RD   Tena Juan J JJ   Rigby Peter W J PWJ   Devos Damien P DP   Gómez-Skarmeta Jose L JL   Carvajal Jaime J JJ  

Genome biology 20170614 1

The organisation of vertebrate genomes into topologically associating domains (TADs) is believed to facilitate the regulation of the genes located within them. A remaining question is whether TAD organisation is achieved through the interactions of the regulatory elements within them or if these interactions are favoured by the pre-existence of TADs. If the latter is true, the fusion of two independent TADs should result in the rewiring of the transcriptional landscape and the generation of ecto  ...[more]

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