| http://purl.uniprot.org/citations/37272752 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/37272752 | http://www.w3.org/2000/01/rdf-schema#comment | "Hypermethylation of CpG islands (CGI) is a common feature of cancer cells and predominantly affects Polycomb-associated genomic regions. Elucidating the underlying mechanisms leading to DNA hypermethylation in human cancer could help identify chemoprevention strategies. Here, we evaluated the role of Polycomb complexes and 5-methylcytosine (5mC) oxidases in protecting CGIs from DNA methylation and observed that four genes coding for components of Polycomb repressive complex 1 (PRC1) are downregulated in tumors. Inactivation of RYBP, a key activator of variant PRC1 complexes, in combination with all three 5mC oxidases (TET proteins) in nontumorigenic bronchial epithelial cells led to widespread hypermethylation of Polycomb-marked CGIs affecting almost 4,000 target genes, which closely resembled the DNA hypermethylation landscape observed in human squamous cell lung tumors. The RYBP- and TET-deficient cells showed methylation-associated aberrant regulation of cancer-relevant pathways, including defects in the Hippo tumor suppressor network. Notably, the quadruple knockout cells acquired a transformed phenotype, including anchorage-independent growth and formation of squamous cell carcinomas in mice. This work provides a mechanism promoting hypermethylation of CGIs and shows that such hypermethylation can lead to cell transformation. The breakdown of a two-pronged protection mechanism can be a route towards genome-wide hypermethylation of CGIs in tumors.SignificanceDysfunction of the Polycomb component RYBP in combination with loss of 5-methylcytosine oxidases promotes widespread hypermethylation of CpG islands in bronchial cells and induces tumorigenesis, resembling changes seen in human lung tumors."xsd:string |
| http://purl.uniprot.org/citations/37272752 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-23-0269"xsd:string |
| http://purl.uniprot.org/citations/37272752 | http://purl.uniprot.org/core/author | "Johnson J."xsd:string |
| http://purl.uniprot.org/citations/37272752 | http://purl.uniprot.org/core/author | "Huang Z."xsd:string |
| http://purl.uniprot.org/citations/37272752 | http://purl.uniprot.org/core/author | "Cui W."xsd:string |
| http://purl.uniprot.org/citations/37272752 | http://purl.uniprot.org/core/author | "Hostetter G."xsd:string |
| http://purl.uniprot.org/citations/37272752 | http://purl.uniprot.org/core/author | "Pfeifer G.P."xsd:string |
| http://purl.uniprot.org/citations/37272752 | http://purl.uniprot.org/core/author | "Lau K.H."xsd:string |
| http://purl.uniprot.org/citations/37272752 | http://purl.uniprot.org/core/author | "Jin S.G."xsd:string |
| http://purl.uniprot.org/citations/37272752 | http://purl.uniprot.org/core/date | "2023"xsd:gYear |
| http://purl.uniprot.org/citations/37272752 | http://purl.uniprot.org/core/name | "Cancer Res"xsd:string |
| http://purl.uniprot.org/citations/37272752 | http://purl.uniprot.org/core/pages | "2480-2495"xsd:string |
| http://purl.uniprot.org/citations/37272752 | http://purl.uniprot.org/core/title | "Deficiency of the Polycomb Protein RYBP and TET Methylcytosine Oxidases Promotes Extensive CpG Island Hypermethylation and Malignant Transformation."xsd:string |
| http://purl.uniprot.org/citations/37272752 | http://purl.uniprot.org/core/volume | "83"xsd:string |
| http://purl.uniprot.org/citations/37272752 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/37272752 |
| http://purl.uniprot.org/citations/37272752 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/37272752 |
| http://purl.uniprot.org/uniprot/#_Q8N488-mappedCitation-37272752 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37272752 |
| http://purl.uniprot.org/uniprot/#_L8ECE1-mappedCitation-37272752 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/37272752 |
| http://purl.uniprot.org/uniprot/Q8N488 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/37272752 |
| http://purl.uniprot.org/uniprot/L8ECE1 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/37272752 |