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Epigenetic alterations in TRAMP mice: epigenome DNA methylation profiling using MeDIP-seq
Wenji Li1,2, Ying Huang1,2,3, Davit Sargsyan1,2,3
11Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, The State University of New Jersey, Piscataway, NJ 08854 USA.
Cell & Bioscience
|January 19, 2018
Summary
This study reveals widespread DNA methylation changes in prostate cancer using the TRAMP mouse model. These epigenetic alterations in genes and pathways offer new targets for prostate cancer treatment and prevention strategies.
Area of Science:
- Epigenetics
- Genomics
- Cancer Biology
Background:
- Prostate cancer is a significant health concern.
- Understanding the epigenetic landscape of prostate cancer is crucial for developing new therapies.
- The transgenic adenocarcinoma of the mouse prostate (TRAMP) model offers a valuable platform for studying prostate cancer development.
Purpose of the Study:
- To investigate the genome-wide DNA methylation profile in prostate cancer using the TRAMP model.
- To identify aberrant CpG hyper- and hypo-methylation patterns.
- To analyze the crosstalk among targeted genes and their associated functional pathways.
Main Methods:
- DNA methylation profiles were analyzed using methylated DNA immunoprecipitation (MeDIP) followed by next-generation sequencing (MeDIP-seq).
- Ingenuity Pathway Analysis (IPA) software was employed for canonical pathways, diseases, and function analyses.
- Methylation-specific primers (MSP) and quantitative PCR (qPCR) were used for validation of key genes.
Main Results:
- Extensive aberrant CpG hyper- and hypo-methylation was observed in TRAMP mice.
- A significant change in CpG methylation was identified in 2147 genes between TRAMP and control mice.
- Altered methylation profiles were noted in pathways related to cAMP response element-binding protein (CREB), histone deacetylase 2 (HDAC2), glutathione S-transferase pi (GSTP1), and polyubiquitin-C (UBC).
Conclusions:
- This study provides the first MeDIP-seq and IPA analysis of the TRAMP model, offering novel insights into prostate cancer epigenetics.
- Identified DNA methylation changes highlight potential new avenues for biomarker development.
- Epigenetic studies, particularly DNA methylation, are promising for advancing prostate cancer treatment and prevention strategies.
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