دورية أكاديمية
STAG2 loss-of-function affects short-range genomic contacts and modulates the basal-luminal transcriptional program of bladder cancer cells.
| العنوان: | STAG2 loss-of-function affects short-range genomic contacts and modulates the basal-luminal transcriptional program of bladder cancer cells. |
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| المؤلفون: | Richart, Laia, Lapi, Eleonora, Pancaldi, Vera, Cuenca-Ardura, Mirabai, Pau, Enrique Carrillo-de-Santa, Madrid-Mencía, Miguel, Neyret-Kahn, Hélène, Radvanyi, François, Rodríguez, Juan Antonio, Cuartero, Yasmina, Serra, François, Le Dily, François, Valencia, Alfonso, Marti-Renom, Marc A, Real Arribas, Francisco |
| المساهمون: | Asociación Española Contra el Cáncer, Institut National de la Santé et de la Recherche Médicale (Francia), Fondation Toulouse Cancer Sante, Ministerio de Ciencia, Innovación y Universidades (España), Institució Catalana de Recerca i Estudis Avançats, Government of Catalonia (España), Unión Europea. Comisión Europea, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2021 |
| المجموعة: | REPISALUD (REPositorio Institucional en SALUD del Instituto de Salud Carlos III - ISCIII) |
| مصطلحات موضوعية: | COHESIN COMPLEX, MUTATIONS, GENES, REVEALS, INACTIVATION, PRINCIPLES, COMPONENTS, ANEUPLOIDY, ELEMENTS, DOMAIN, Loss of Function Mutation, Transcription, Genetic, Base Sequence, Cell Cycle Proteins, Cell Line, Tumor, Chromatin, Chromosomal Proteins, Non-Histone, DNA, Neoplasm, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Ontology, HEK293 Cells, Histones, Humans, Molecular Sequence Annotation |
| الوصف: | Cohesin exists in two variants containing STAG1 or STAG2. STAG2 is one of the most mutated genes in cancer and a major bladder tumor suppressor. Little is known about how its inactivation contributes to tumorigenesis. Here, we analyze the genomic distribution of STAG1 and STAG2 and perform STAG2 loss-of-function experiments using RT112 bladder cancer cells; we then analyze the genomic effects by integrating gene expression and chromatin interaction data. Functional compartmentalization exists between the cohesin complexes: cohesin-STAG2 displays a distinctive genomic distribution and mediates short and mid-ranged interactions that engage genes at higher frequency than those established by cohesin-STAG1. STAG2 knockdown results in down-regulation of the luminal urothelial signature and up-regulation of the basal transcriptional program, mirroring differences between STAG2-high and STAG2-low human bladder tumors. This is accompanied by rewiring of DNA contacts within topological domains, while compartments and domain boundaries remain refractive. Contacts lost upon depletion of STAG2 are assortative, preferentially occur within silent chromatin domains, and are associated with de-repression of lineage-specifying genes. Our findings indicate that STAG2 participates in the DNA looping that keeps the basal transcriptional program silent and thus sustains the luminal program. This mechanism may contribute to the tumor suppressor function of STAG2 in the urothelium. ; Fundacion Cientifica de la Asociacion Espanola Contra el Cancer (to F.X.R., E.L., in part); V.P. is supported by INSERM, the Fondation Toulouse Cancer Sante and Pierre Fabre Research Institute as part of the Chair of Bioinformatics in Oncology of the CRCT; Bioinfo4women programme at the Barcelona Supercomputing Center; European Union's H2020 Framework Programme through the ERC [609989 to M.A.M.-R., in part]; Spanish Ministerio de Ciencia, Innovaci ' on y Universidades [BFU2017-85926P to M.A.M.-R.]; C.N.I.O. is supported by Ministerio de Ciencia, ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1362-4962 |
| العلاقة: | Publisher's version; https://doi.org/10.1093/nar/gkab864Test.; info:eu-repo/grantAgreement/BFU2017-85926P; info:eu-repo/grantAgreement/SEV-2015-0510; info:eu-repo/grantAgreement/SEV-2012-0208; Nucleic Acids Res . 2021 ;49(19):11005-11021.; http://hdl.handle.net/20.500.12105/13723Test; Nucleic acids research |
| DOI: | 10.1093/nar/gkab864 |
| الإتاحة: | https://doi.org/20.500.12105/13723Test https://doi.org/10.1093/nar/gkab864Test https://hdl.handle.net/20.500.12105/13723Test |
| حقوق: | http://creativecommons.org/licenses/by-nc-sa/4.0Test/ ; Atribución-NoComercial-CompartirIgual 4.0 Internacional ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.B9E245BA |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 13624962 |
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| DOI: | 10.1093/nar/gkab864 |