ArticleNucleic acids research2021
STAG2 loss-of-function affects short-range genomic contacts and modulates the basal-luminal transcriptional program of bladder cancer cells.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Origins and consequences of oncogenic 3D chromatin remodelling.Nature reviews. Cancer · 2026Review
- Rapid reduction in global chromatin loop size after acute STAG2 reconstitution in human cancer cells.bioRxiv : the preprint server for biology · 2026Article
- STAG2-truncating variants reveal a mosaic STAG2 inactivation pattern and compensatory mechanisms involving cohesin complex remodeling.iScience · 2025Article
- STAG2 expression imparts distinct therapeutic vulnerabilities in muscle-invasive bladder cancer cells.Oncogenesis · 2025Article
- Emerging roles of cohesin-STAG2 in cancer.Oncogene · 2025Review
- A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis.The Journal of experimental medicine · 2025Article
- STAG2 mutations in the normal colon induce upregulation of oncogenic pathways in neighbouring wildtype cells.PloS one · 2025Article
- STAG2 regulates polycomb and differentiation in urothelial precursors and bladder cancer.PloS one · 2025Article
- Untangling the loops ofLeukemia & lymphoma · 2025Review
- STAG2 loss in Ewing sarcoma alters enhancer-promoter contacts dependent and independent of EWS::FLI1.EMBO reports · 2024Article
- Review
- Bladder cancer.Nature reviews. Disease primers · 2023Review
- Multiomic analysis of cohesin reveals that ZBTB transcription factors contribute to chromatin interactions.Nucleic acids research · 2023Article
- Article
- Different NIPBL requirements of cohesin-STAG1 and cohesin-STAG2.Nature communications · 2023Article
- Identification of STAG2-Mutant Bladder Cancers by Immunohistochemistry.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Contribution of variant subunits and associated factors to genome-wide distribution and dynamics of cohesin.Epigenetics & chromatin · 2022Article
- A global high-density chromatin interaction network reveals functional long-range and trans-chromosomal relationships.Genome biology · 2022Article
- Stromal Antigen 2 Deficiency Induces Interferon Responses and Restricts Porcine Deltacoronavirus Infection.Viruses · 2022Article
- STAG2 regulates interferon signaling in melanoma via enhancer loop reprogramming.Nature communications · 2022Article
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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