دورية أكاديمية
EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma
| العنوان: | EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma |
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| المؤلفون: | Moller E., Praz V., Rajendran S., Dong R., Cauderay A., Xing Y. -H., Lee L., Fusco C., Broye L. C., Cironi L., Iyer S., Rengarajan S., Awad M. E., Naigles B., Letovanec I., Ormas N., Finzi G., La Rosa S., Sessa F., Chebib I., Petur Nielsen G., Digklia A., Spentzos D., Cote G. M., Choy E., Aryee M., Stamenkovic I., Boulay G., Rivera M. N., Riggi N. |
| المساهمون: | Moller, E., Praz, V., Rajendran, S., Dong, R., Cauderay, A., Xing, Y. -H., Lee, L., Fusco, C., Broye, L. C., Cironi, L., Iyer, S., Rengarajan, S., Awad, M. E., Naigles, B., Letovanec, I., Ormas, N., Finzi, G., La Rosa, S., Sessa, F., Chebib, I., Petur Nielsen, G., Digklia, A., Spentzos, D., Cote, G. M., Choy, E., Aryee, M., Stamenkovic, I., Boulay, G., Rivera, M. N., Riggi, N. |
| سنة النشر: | 2022 |
| المجموعة: | IRInSubria - Institutional Repository Insubria (Università degli Studi dell’Insubria) |
| مصطلحات موضوعية: | Carcinogenesi, Chromatin, Human, Oncogene Proteins, Fusion, Oncogene, RNA-Binding Protein EWS, Sarcoma, Clear Cell, Soft Tissue Neoplasms |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | ELETTRONICO |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/35477713; info:eu-repo/semantics/altIdentifier/wos/WOS:000788592600006; volume:13; issue:1; firstpage:1; lastpage:18; numberofpages:18; journal:NATURE COMMUNICATIONS; http://hdl.handle.net/11383/2134668Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85128908819 |
| DOI: | 10.1038/s41467-022-29910-4 |
| الإتاحة: | https://doi.org/10.1038/s41467-022-29910-4Test http://hdl.handle.net/11383/2134668Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.5239EBEC |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-022-29910-4 |
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