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EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma [RNA-seq]

ABSTRACT: EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma [RNA-seq]

PROVIDER: PRJNA747008 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15164203_1.fastq.gz	Fastqsanger.gz
	SRR15164203_2.fastq.gz	Fastqsanger.gz
	SRR15164204.fastq.gz	Fastqsanger.gz
	SRR15164205_1.fastq.gz	Fastqsanger.gz
	SRR15164205_2.fastq.gz	Fastqsanger.gz

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EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma [RNA-seq]

Project description:Chimeric proteins resulting from chromosomal translocations play a major role as driver oncogenes in cancer. Among them, fusions between EWSR1 and a set of transcription factors (TFs) generate oncogenes with powerful chromatin regulatory activities, capable of establishing complex gene expression programs. However, specific EWSR1 fusion proteins have been implicated in distinct tumor types, suggesting an enhancement of their functional properties by permissive precursor cells. Here we combined functional epigenomics with nuclear topology mapping to define the epigenetic and 3D connectivity landscape of Clear Cell Sarcoma (CCS), one of the most aggressive forms of human cancer, driven by the EWSR1-ATF1 fusion gene. We find that EWSR1-ATF1 display a distinctive binding pattern that depends on the EWSR1 prion-like domain, and is divergent from wild type ATF1, despite the physical interaction between wt and EWSR1-ATF1 proteins. This cooperativity promotes ATF1 retargeting to new distal sites, leading to chromatin activation and the establishment of a 3D network that controls oncogenic and differentiation signatures shared with primary CCS tumors. Conversely, EWSR1-ATF1 depletion results in a marked reconfiguration of 3D connectivity, including the emergence of a new set of connections controlling neural crest-related developmental programs. Accordingly, interrogation of more than 160,000 single cell expression profiles from the human skin atlas reveals loss of EWSR1-ATF1 expression to induce a more differentiated tumor cell state. Taken together, our study uncovers the cooperativity network of EWSR1-ATF1, delineates the molecular underpinnings of its epigenetic function in CCS, and points to precursor cells along the Schwann cell-melanocytic axis as a candidate origin for these tumors.

2022-03-04 | GSE180196 | GEO

EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma [ATAC-Seq]

2022-03-04 | GSE180183 | GEO

EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma [HiChIP-seq]

Project description:Chimeric proteins resulting from chromosomal translocations play a major role as driver oncogenes in cancer. Among them, fusions between EWSR1 and a set of transcription factors (TFs) generate oncogenes with powerful chromatin regulatory activities, capable of establishing complex gene expression programs. However, specific EWSR1 fusion proteins have been implicated in distinct tumor types, suggesting an enhancement of their functional properties by permissive precursor cells. Here we combined functional epigenomics with nuclear topology mapping to define the epigenetic and 3D connectivity landscape of Clear Cell Sarcoma (CCS), one of the most aggressive forms of human cancer, driven by the EWSR1-ATF1 fusion gene. We find that EWSR1-ATF1 display a distinctive binding pattern that depends on the EWSR1 prion-like domain, and is divergent from wild type ATF1, despite the physical interaction between wt and EWSR1-ATF1 proteins. This cooperativity promotes ATF1 retargeting to new distal sites, leading to chromatin activation and the establishment of a 3D network that controls oncogenic and differentiation signatures shared with primary CCS tumors. Conversely, EWSR1-ATF1 depletion results in a marked reconfiguration of 3D connectivity, including the emergence of a new set of connections controlling neural crest-related developmental programs. Accordingly, interrogation of more than 160’000 single cell expression profiles from the human skin atlas reveals loss of EWSR1-ATF1 expression to induce a more differentiated tumor cell state. Taken together, our study uncovers the cooperativity network of EWSR1-ATF1, delineates the molecular underpinnings of its epigenetic function in CCS, and points to precursor cells along the Schwann cell-melanocytic axis as a candidate origin for these tumors.

2022-03-04 | GSE180194 | GEO

EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma [ChIP-Seq]

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EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma

Project description:EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma

| PRJNA747002 | ENA

EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma [ATAC-Seq]

Project description:EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma [ATAC-Seq]

| PRJNA746990 | ENA

EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma [ChIP-Seq]

Project description:EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma [ChIP-Seq]

| PRJNA746997 | ENA

EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma [HiChIP-seq]

Project description:EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma [HiChIP-seq]

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EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma.

Project description:Oncogenic fusion proteins generated by chromosomal translocations play major roles in cancer. Among them, fusions between EWSR1 and transcription factors generate oncogenes with powerful chromatin regulatory activities, capable of establishing complex gene expression programs in permissive precursor cells. Here we define the epigenetic and 3D connectivity landscape of Clear Cell Sarcoma, an aggressive cancer driven by the EWSR1-ATF1 fusion gene. We find that EWSR1-ATF1 displays a distinct DNA binding pattern that requires the EWSR1 domain and promotes ATF1 retargeting to new distal sites, leading to chromatin activation and the establishment of a 3D network that controls oncogenic and differentiation signatures observed in primary CCS tumors. Conversely, EWSR1-ATF1 depletion results in a marked reconfiguration of 3D connectivity, including the emergence of regulatory circuits that promote neural crest-related developmental programs. Taken together, our study elucidates the epigenetic mechanisms utilized by EWSR1-ATF1 to establish regulatory networks in CCS, and points to precursor cells in the neural crest lineage as candidate cells of origin for these tumors.

| S-EPMC9046276 | biostudies-literature

Gene signatures of sarcoma tumors with EWSR1-CREB fusion [RNA-seq]

Project description:We report RNA-seq for rare 3 rare entities of sarcoma tumors (AFH, CCS and GI-CCS) expressing the EWSR1-CREB1 and EWSR1-ATF1 oncogenic fusion

2021-08-18 | GSE168561 | GEO

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