{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE294nnn/GSE294308/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE294308"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"5-hydroxymethylcytosine deposition mediates Polycomb Repressive Complex 2 function in MYCN-amplified neuroblastoma [RNA-seq]","description":"MYCN-amplification is a strong predictor of poor prognosis in neuroblastoma, an embryonal malignancy that accounts for 15% of pediatric cancer deaths. Here, we found that MYCN-amplified neuroblastoma tumors have increased 5-hydroxymethylcytosine (5-hmC) deposition on Polycomb Repressive Complex 2 (PRC2) target genes. 5-hmC and H3K27me3, a catalytic product of PRC2, directly co-localize at the nucleosomal level in MYCN-amplified neuroblastoma. Genes with co-localization of 5-hmC/H3K27me3 are involved in development related pathways and are transcriptionally repressed in MYCN-amplified neuroblastoma. Chemical and genetic inhibition of 5-hmC deposition results in a loss of H3K27me3 deposition on protein-coding genes. Furthermore, 5-hmC deposition predisposes H3K27me3 marked genes to transcriptional activation upon PRC2 inhibition with tazemetostat. Low expression of genes marked by 5-hmC/H3K27me3 is associated with poor clinical outcome. Our results suggest that 5-hmC/H3K27me3 co-operate to repress mediators of development highlighting a novel link between DNA modifications and chromatin modifications with potential therapeutic implications in MYCN-amplified neuroblastoma.","dates":{"publication":"2026/05/12"},"accession":"GSE294308","cross_references":{"GSM":["GSM8902191","GSM8902190","GSM8902193","GSM8902192","GSM8902188","GSM8902198","GSM8902187","GSM8902189","GSM8902195","GSM8902194","GSM8902186","GSM8902197","GSM8902185","GSM8902196"],"GPL":["24676"],"GSE":["294308"],"taxon":["Homo sapiens"]}}