GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE294nnn/GSE294308/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE294308GEOGSEfalse5-hydroxymethylcytosine deposition mediates Polycomb Repressive Complex 2 function in MYCN-amplified neuroblastoma [RNA-seq]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.2026/05/12GSE294308GSM8902191GSM8902190GSM8902193GSM8902192GSM8902188GSM8902198GSM8902187GSM8902189GSM8902195GSM8902194GSM8902197GSM8902186GSM8902185GSM890219624676294308Homo sapiens