2026-06-14T03:54:27Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/137232024-11-30T00:25:57Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Richart, Laia
author
Lapi, Eleonora
author
Pancaldi, Vera
author
Cuenca-Ardura, Mirabai
author
Pau, Enrique Carrillo-de-Santa
author
Madrid-Mencía, Miguel
author
Neyret-Kahn, Hélène
author
Radvanyi, François
author
Rodríguez, Juan Antonio
author
Cuartero, Yasmina
author
Serra, François
author
Le Dily, François
author
Valencia, Alfonso
author
Marti-Renom, Marc A
author
Real Arribas, Francisco
funder
Asociación Española Contra el Cáncer
funder
Institut National de la Santé et de la Recherche Médicale (Francia)
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Institució Catalana de Recerca i Estudis Avançats
funder
Government of Catalonia (España)
funder
Unión Europea. Comisión Europea
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Fondation Toulouse Cancer Sante
2022-03-04T10:39:21Z
2022-03-04T10:39:21Z
2021-11-08
Nucleic Acids Res . 2021 ;49(19):11005-11021.
10.1093/nar/gkab864
1362-4962
Nucleic acids research
34648034
http://hdl.handle.net/20.500.12105/13723
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.
eng
COHESIN COMPLEX
MUTATIONS
GENES
REVEALS
INACTIVATION
PRINCIPLES
COMPONENTS
ANEUPLOIDY
ELEMENTS
DOMAIN
STAG2 loss-of-function affects short-range genomic contacts and modulates the basal-luminal transcriptional program of bladder cancer cells.
journal article
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STAG2loss-of-functionaffectsshort_2021.pdf.txt
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