GEO series
Crosstalk between the polycomb repressive complex 2 and DNA methylation mediates neuroendocrine prostate cancer lineage plasticity [ChIP-Seq]
GSE289247
Homo sapiens; Mus musculus
Genome binding/occupancy profiling by high throughput sequencing
35 samples
Submitted 2025/11/25
Platform GPL24247Platform GPL24676
Summary
Acquired changes in DNA methylation have been proposed as a mechanism underlying epigenetic plasticity in several cancer types. In prostate cancer, methylation changes are dynamic, with preclinical studies pointing to a tumor suppressor role of the DNA methyltransferase DNMT1 in early stage, in contrast to an oncogenic function of DNMT1 in later stage. The importance of DNA methylation dynamics during normal development and cell lineage fate decisions also points to DNA methylation having a critical function in lineage plasticity, yet the mechanisms by which DNA methylation changes drives lineage transitions in prostate cancer is not well understood. DNA methylation can directly repress gene expression but also cooperate with other epigenetic pathways to modulate downstream transcriptional activity. The enhancer of zeste homolog 2 (EZH2) protein is a subunit of the polycomb repressive complex 2 (PRC2) and catalyzer of the repressive histone 3 lysine 27 tri-methylation (H3K27me3) mark that also acts to suppress downstream transcriptional activity and has also been implicated in lineage plasticity. EZH2 is overexpressed in castration-resistant prostate cancer (CRPC) including NEPC and is an emerging therapeutic target. Although, the compensatory relationship between DNA methylation and EZH2 has been shown in embryonic stem cell studies and in some cancer types during acquired treatment resistance or immune evasion, how DNA methylation and EZH2/PRC2 interact to modulate prostate cancer lineage plasticity has not been characterized. In this study, we address the potential crosstalk between epigenetic pathways in advanced prostate cancer and demonstrate how DNA methylation and H3K27me3 profiles overlap and cooperate to reprogram the epigenome during prostate cancer lineage plasticity. Using both mouse and patient-derived models, we highlight the compensatory roles of these two repressive machineries during progression of CRPC towards a NE-lineage state. We predict their specific impact on NEPC progression by assessing the associated molecular alterations following genetic and pharmacological perturbations of each.
Published in
Singh R, Venkadakrishnan VB, Imada E et al.
· Nature communications 2026
· PMID 41720768
· doi:10.1038/s41467-026-69308-0
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE289247_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 35 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1222007 and SRA study SRP563080. Searching any of these in the dataset finder brings you back here.
Study design
35 conditions, each sampled once — no replicated groups
Read from 35 sample titles: 35 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8787709 Decitabine_PDX48_H3K27me3-Input
- GSM8787710 Decitabine_PDX48_H3K27me3
- GSM8787711 Decitabine_PDX50_H3K27me3-Input
- GSM8787712 Decitabine_PDX50_H3K27me3
- GSM8787713 Decitabine_PDX58_H3K27me3-Input
- GSM8787714 Decitabine_PDX58_H3K27me3
- GSM8787715 Vehicle_PDX51_H3K27me3-Input
- GSM8787716 Vehicle_PDX51_H3K27me3
- GSM8787717 Vehicle_PDX55_H3K27me3-Input
- GSM8787718 Vehicle_PDX55_H3K27me3
- GSM8787719 Vehicle_PDX61_H3K27me3-Input
- GSM8787720 Vehicle_PDX61_H3K27me3
- GSM8787721 Decitabine_PDX48_H3K4me3-Input
- GSM8787722 Decitabine_PDX48_H3K4me3
- GSM8787723 Decitabine_PDX53_H3K4me3-Input
- GSM8787724 Decitabine_PDX53_H3K4me3
- GSM8787725 Vehicle_PDX55_H3K4me3-Input
- GSM8787726 Vehicle_PDX55_H3K4me3
- GSM8787727 Vehicle_PDX61_H3K4me3-Input
- GSM8787728 Vehicle_PDX61_H3K4me3
- GSM8787729 PRN_Adeno_M2229_H3K4ME3
- GSM8787730 PRN_Adeno_M2229_Input
- GSM8787731 PRN_Adeno_M2266-2_H3K27me3
- GSM8787732 PRN_Adeno_M2266-2_H3K4me3
- GSM8787733 PRN_Adeno_M2266-2_Input
- GSM8787734 PRN_Adeno_M5217_H3K27me3
- GSM8787735 PRN_Adeno_M5217_Input
- GSM8787736 PRN_NEPC_M2266-2_H3K4me3
- GSM8787737 PRN_NEPC_M2266-2_Input
- GSM8787738 PRN_NEPC_M3713_H3K27me3
- GSM8787739 PRN_NEPC_M3713_Input
- GSM8787740 PRN_NEPC_M3733_H3K27me3-Input
- GSM8787741 PRN_NEPC_M3733_H3K27me3
- GSM8787742 PRN_NEPC_M3733_H3K4me3-Input
- GSM8787743 PRN_NEPC_M3733_H3K4me3
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