PLX028716

GSE128287: Reprogramming to human nave pluripotency mirrors pan-cancer DNA hypermethylation [RNA-seq]

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Aberrant DNA hypermethylation of promoter CpG islands in the context of a hypomethylated genome is a hallmark of cancer. Thus far there is no human experimental model available to mechanistically investigate this phenomenon. Here we show that upon reprogramming of human embryonic stem cells to the nave state, the acquisition of a globally hypomethylated genome is accompanied by hypermethylation of a subset of bivalent promoter CpG islands, resulting in a DNA methylome comparable to the human inner cell mass. We show that de novo methylation is carried out by DNMT3A and coordinated by the transcription factor network. We further show that the subset of bivalent sites that become hypermethyated are functionally distinct, with an enrichment in developmental genes, and demonstrate that this is mirrored in DNA hypermethylation patterns across cancer types, suggesting that common mechanisms may be responsible. We propose a wider utility of this experimental system to understand pre-malignant cancer-associated processes. SOURCE: Hemalvi Patani (hemalvi_179@hotmail.com) - Barts Cancer Institute