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Cell Biosci. 2018 Jan 12;8:3. doi: 10.1186/s13578-018-0201-y. eCollection 2018.

Epigenetic alterations in TRAMP mice: epigenome DNA methylation profiling using MeDIP-seq.

Li W#1,2, Huang Y#1,2,3, Sargsyan D1,2,3, Khor TO1,2, Guo Y1,2,3, Shu L1,2, Yang AY1,2,3, Zhang C1,2,3, Paredes-Gonzalez X1,2,3, Verzi M4, Hart RP5, Kong AN1,2.

Author information

1Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, The State University of New Jersey, Piscataway, NJ 08854 USA.
2Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854 USA.
3Graduate Program in Pharmaceutical Sciences, Ernest Mario School of Pharmacy, The State University of New Jersey, Piscataway, NJ 08854 USA.
4Department of Genetics, The State University of New Jersey, Piscataway, NJ 08854 USA.
5Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 USA.
Contributed equally



We investigated the genomic DNA methylation profile of prostate cancer in transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model and to analyze the crosstalk among targeted genes and the related functional pathways.


Prostate DNA samples from 24-week-old TRAMP and C57BL/6 male mice were isolated. The DNA methylation profiles were analyzed by methylated DNA immunoprecipitation (MeDIP) followed by next-generation sequencing (MeDIP-seq). Canonical pathways, diseases and function and network analyses of the different samples were then performed using the Ingenuity® Pathway Analysis (IPA) software. Some target genes with significant difference in methylation were selected for validation using methylation specific primers (MSP) and qPCR.


TRAMP mice undergo extensive aberrant CpG hyper- and hypo-methylation. There were 2147 genes with a significant (log2-change ≥ 2) change in CpG methylation between the two groups, as mapped by the IPA software. Among these genes, the methylation of 1105 and 1042 genes was significantly decreased and increased, respectively, in TRAMP prostate tumors. The top associated disease identified by IPA was adenocarcinoma; however, the cAMP response element-binding protein (CREB)-, histone deacetylase 2 (HDAC2)-, glutathione S-transferase pi (GSTP1)- and polyubiquitin-C (UBC)-related pathways showed significantly altered methylation profiles based on the canonical pathway and network analyses. MSP and qPCR results of genes of interests corroborated with MeDIP-seq findings.


This is the first MeDIP-seq with IPA analysis of the TRAMP model to provide novel insight into the genome-wide methylation profile of prostate cancer. Studies on epigenetics, such as DNA methylation, will potentially provide novel avenues and strategies for further development of biomarkers targeted for treatment and prevention approaches for prostate cancer.


DNA methylation; Epigenetics; MeDIP-seq; Prostate cancer; TRAMP

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