Epigenetic alterations in TRAMP mice: epigenome DNA methylation profiling using MeDIP-seq
Abstract Purpose 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. Methods Prostate DNA samples from 24-week-old TRAMP a...
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doaj-36008436c6f24ebeaed303d0096263532020-11-25T02:47:38ZengBMCCell & Bioscience2045-37012018-01-018111910.1186/s13578-018-0201-yEpigenetic alterations in TRAMP mice: epigenome DNA methylation profiling using MeDIP-seqWenji Li0Ying Huang1Davit Sargsyan2Tin Oo Khor3Yue Guo4Limin Shu5Anne Yuqing Yang6Chengyue Zhang7Ximena Paredes-Gonzalez8Michael Verzi9Ronald P. Hart10Ah-Ng Kong11Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, The State University of New JerseyCenter for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, The State University of New JerseyCenter for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, The State University of New JerseyCenter for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, The State University of New JerseyCenter for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, The State University of New JerseyCenter for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, The State University of New JerseyCenter for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, The State University of New JerseyCenter for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, The State University of New JerseyCenter for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, The State University of New JerseyDepartment of Genetics, The State University of New JerseyDepartment of Cell Biology and Neuroscience, Rutgers, The State University of New JerseyCenter for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, The State University of New JerseyAbstract Purpose 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. Methods 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. Results 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. Conclusions 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.http://link.springer.com/article/10.1186/s13578-018-0201-yMeDIP-seqEpigeneticsDNA methylationTRAMPProstate cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wenji Li Ying Huang Davit Sargsyan Tin Oo Khor Yue Guo Limin Shu Anne Yuqing Yang Chengyue Zhang Ximena Paredes-Gonzalez Michael Verzi Ronald P. Hart Ah-Ng Kong |
spellingShingle |
Wenji Li Ying Huang Davit Sargsyan Tin Oo Khor Yue Guo Limin Shu Anne Yuqing Yang Chengyue Zhang Ximena Paredes-Gonzalez Michael Verzi Ronald P. Hart Ah-Ng Kong Epigenetic alterations in TRAMP mice: epigenome DNA methylation profiling using MeDIP-seq Cell & Bioscience MeDIP-seq Epigenetics DNA methylation TRAMP Prostate cancer |
author_facet |
Wenji Li Ying Huang Davit Sargsyan Tin Oo Khor Yue Guo Limin Shu Anne Yuqing Yang Chengyue Zhang Ximena Paredes-Gonzalez Michael Verzi Ronald P. Hart Ah-Ng Kong |
author_sort |
Wenji Li |
title |
Epigenetic alterations in TRAMP mice: epigenome DNA methylation profiling using MeDIP-seq |
title_short |
Epigenetic alterations in TRAMP mice: epigenome DNA methylation profiling using MeDIP-seq |
title_full |
Epigenetic alterations in TRAMP mice: epigenome DNA methylation profiling using MeDIP-seq |
title_fullStr |
Epigenetic alterations in TRAMP mice: epigenome DNA methylation profiling using MeDIP-seq |
title_full_unstemmed |
Epigenetic alterations in TRAMP mice: epigenome DNA methylation profiling using MeDIP-seq |
title_sort |
epigenetic alterations in tramp mice: epigenome dna methylation profiling using medip-seq |
publisher |
BMC |
series |
Cell & Bioscience |
issn |
2045-3701 |
publishDate |
2018-01-01 |
description |
Abstract Purpose 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. Methods 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. Results 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. Conclusions 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. |
topic |
MeDIP-seq Epigenetics DNA methylation TRAMP Prostate cancer |
url |
http://link.springer.com/article/10.1186/s13578-018-0201-y |
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