ArticleScientific reports2021
Dynamic patterns of DNA methylation in the normal prostate epithelial differentiation program are targets of aberrant methylation in prostate cancer.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Towards implementation of precision medicine biomarkers in early detection and prognostication of prostate cancer.Cancer metastasis reviews · 2026Review
- Prostate cancer epigenetics - from pathophysiology to clinical application.Nature reviews. Urology · 2025Review
- MethBank 4.0: an updated database of DNA methylation across a variety of species.Nucleic acids research · 2023Article
- Epigenetic Inheritance From Normal Origin Cells Can Determine the Aggressive Biology of Tumor-Initiating Cells and Tumor Heterogeneity.Cancer control : journal of the Moffitt Cancer CenterArticle
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6 authors.
Funding
Abstract
Understanding the epigenetic control of normal differentiation programs might yield principal information about critical regulatory states that are disturbed in cancer. We utilized the established non-malignant HPr1-AR prostate epithelial cell model that upon androgen exposure commits to a luminal cell differentiation trajectory from that of a basal-like state. We profile the dynamic transcriptome associated with this transition at multiple time points (0 h, 1 h, 24 h, 96 h), and confirm that expression patterns are strongly indicative of a progressive basal to luminal cell differentiation program based on human expression signatures. Furthermore, we establish dynamic patterns of DNA methylation associated with this program by use of whole genome bisulfite sequencing (WGBS). Expression patterns associated with androgen induced luminal cell differentiation were found to have significantly elevated DNA methylation dynamics. Shifts in methylation profiles were strongly associated with Polycomb repressed regions and to promoters associated with bivalency, and strongly enriched for binding motifs of AR and MYC. Importantly, we found that dynamic DNA methylation patterns observed in the normal luminal cell differentiation program were significant targets of aberrant methylation in prostate cancer. These findings suggest that the normal dynamics of DNA methylation in luminal differentiation contribute to the aberrant methylation patterns in prostate cancer.
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