A pan-cancer analysis of CpG Island gene regulation reveals extensive plasticity within Polycomb target genes.

ABSTRACT: 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

SUBMITTER: Zheng Y 

PROVIDER: S-EPMC8087678 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature