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A pan-cancer analysis of CpG Island gene regulation reveals extensive plasticity within Polycomb target genes.
- Source :
- Nature Communications; 4/30/2021, Vol. 12 Issue 1, p1-16, 16p
- Publication Year :
- 2021
-
Abstract
- CpG Island promoter genes make up more than half of human genes, and a subset regulated by Polycomb-Repressive Complex 2 (PRC2<superscript>+</superscript>-CGI) become DNA hypermethylated and silenced in cancer. Here, we perform a systematic analysis of CGI genes across TCGA cancer types, finding that PRC2<superscript>+</superscript>-CGI genes are frequently prone to transcriptional upregulation as well. These upregulated PRC2<superscript>+</superscript>-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<superscript>+</superscript>-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<superscript>+</superscript>-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. A subset of CpG Island promoter genes are regulated by Polycomb-Repressive Complex 2 (PRC2<superscript>+</superscript>-CGI), which become DNA hypermethylated and silenced in cancer. Here, the authors investigate the transcriptomic and epigenomic characteristics of PRC2-occupied CGI and free CGI across pan-cancer types. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 12
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 150107120
- Full Text :
- https://doi.org/10.1038/s41467-021-22720-0