Nature communications, 2021-04, Vol.12 (1), p.2485-2485, Article 2485
2021
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- Autor(en) / Beteiligte
- Titel
- A pan-cancer analysis of CpG Island gene regulation reveals extensive plasticity within Polycomb target genes
- Ist Teil von
- Nature communications, 2021-04, Vol.12 (1), p.2485-2485, Article 2485
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- CpG Island promoter genes make up more than half of human genes, and a subset regulated by Polycomb-Repressive Complex 2 (PRC2 -CGI) become DNA hypermethylated and silenced in cancer. Here, we perform a systematic analysis of CGI genes across TCGA cancer types, finding that PRC2 -CGI genes are frequently prone to transcriptional upregulation as well. These upregulated PRC2 -CGI genes control important pathways such as Epithelial-Mesenchymal Transition (EMT) and TNFα-associated inflammatory response, and have greater cancer-type specificity than other CGI genes. Using publicly available chromatin datasets and genetic perturbations, we show that transcription factor binding sites (TFBSs) within distal enhancers underlie transcriptional activation of PRC2 -CGI genes, coinciding with loss of the PRC2-associated mark H3K27me3 at the linked promoter. In contrast, PRC2-free CGI genes are predominantly regulated by promoter TFBSs which are common to most cancer types. Surprisingly, a large subset of PRC2 -CGI genes that are upregulated in one cancer type are also hypermethylated/silenced in at least one other cancer type, underscoring the high degree of regulatory plasticity of these genes, likely derived from their complex regulatory control during normal development.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-021-22720-0Titel-ID: cdi_doaj_primary_oai_doaj_org_article_ede738b409a34065ac6b73e8d3099c51
- Format
- –
- Schlagworte
- Binding Sites, Cancer, Cell Line, Tumor, Chromatin, Chromatin - genetics, Chromatin - metabolism, Chromatin Immunoprecipitation Sequencing, CpG Islands, Databases, Genetic, Deoxyribonucleic acid, DNA, DNA Methylation, DNA-Binding Proteins - metabolism, Down-Regulation, Embryonic Stem Cells - metabolism, Enhancer Elements, Genetic, Enhancers, Gene Expression Profiling, Gene Expression Regulation, Neoplastic - genetics, Gene regulation, Genes, Hepatocyte Nuclear Factor 4 - genetics, Hepatocyte Nuclear Factor 4 - metabolism, Histones - metabolism, Humans, Inflammation, Inflammatory response, Mesenchyme, Multigene Family, Neoplasms - genetics, Neoplasms - metabolism, Perturbation, Plastic properties, Plasticity, Polycomb group proteins, Polycomb-Group Proteins - genetics, Polycomb-Group Proteins - metabolism, Principal Component Analysis, Promoter Regions, Genetic, Protein Binding, Signal Transduction - genetics, Transcription activation, Tumor necrosis factor-α, Up-Regulation