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

Wenji Li, Ying Huang, Davit Sargsyan, Tin Oo Khor, Yue Guo, Limin Shu, Anne Yuqing Yang, Chengyue Zhang, Ximena Paredes-Gonzalez, Michael Verzi, Ronald Hart, Ah-Ng Kong

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Article number3
JournalCell and Bioscience
Volume8
Issue number1
DOIs
StatePublished - Jan 12 2018

Fingerprint

Methylation
DNA Fingerprinting
DNA Methylation
Immunoprecipitation
Epigenomics
Transgenic Mice
Prostate
Adenocarcinoma
Genes
DNA
Prostatic Neoplasms
Histone Deacetylase 2
Software
Polyubiquitin
Glutathione S-Transferase pi
Cyclic AMP Response Element-Binding Protein
Biomarkers
Crosstalk
DNA Sequence Analysis
Tumors

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Keywords

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

Cite this

Li, Wenji ; Huang, Ying ; Sargsyan, Davit ; Khor, Tin Oo ; Guo, Yue ; Shu, Limin ; Yang, Anne Yuqing ; Zhang, Chengyue ; Paredes-Gonzalez, Ximena ; Verzi, Michael ; Hart, Ronald ; Kong, Ah-Ng. / Epigenetic alterations in TRAMP mice : Epigenome DNA methylation profiling using MeDIP-seq. In: Cell and Bioscience. 2018 ; Vol. 8, No. 1.
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title = "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 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{\circledR} 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.",
keywords = "DNA methylation, Epigenetics, MeDIP-seq, Prostate cancer, TRAMP",
author = "Wenji Li and Ying Huang and Davit Sargsyan and Khor, {Tin Oo} and Yue Guo and Limin Shu and Yang, {Anne Yuqing} and Chengyue Zhang and Ximena Paredes-Gonzalez and Michael Verzi and Ronald Hart and Ah-Ng Kong",
year = "2018",
month = "1",
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doi = "https://doi.org/10.1186/s13578-018-0201-y",
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Li, W, Huang, Y, Sargsyan, D, Khor, TO, Guo, Y, Shu, L, Yang, AY, Zhang, C, Paredes-Gonzalez, X, Verzi, M, Hart, R & Kong, A-N 2018, 'Epigenetic alterations in TRAMP mice: Epigenome DNA methylation profiling using MeDIP-seq', Cell and Bioscience, vol. 8, no. 1, 3. https://doi.org/10.1186/s13578-018-0201-y

Epigenetic alterations in TRAMP mice : Epigenome DNA methylation profiling using MeDIP-seq. / Li, Wenji; Huang, Ying; Sargsyan, Davit; Khor, Tin Oo; Guo, Yue; Shu, Limin; Yang, Anne Yuqing; Zhang, Chengyue; Paredes-Gonzalez, Ximena; Verzi, Michael; Hart, Ronald; Kong, Ah-Ng.

In: Cell and Bioscience, Vol. 8, No. 1, 3, 12.01.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Epigenetic alterations in TRAMP mice

T2 - Epigenome DNA methylation profiling using MeDIP-seq

AU - Li, Wenji

AU - Huang, Ying

AU - Sargsyan, Davit

AU - Khor, Tin Oo

AU - Guo, Yue

AU - Shu, Limin

AU - Yang, Anne Yuqing

AU - Zhang, Chengyue

AU - Paredes-Gonzalez, Ximena

AU - Verzi, Michael

AU - Hart, Ronald

AU - Kong, Ah-Ng

PY - 2018/1/12

Y1 - 2018/1/12

N2 - 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.

AB - 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.

KW - DNA methylation

KW - Epigenetics

KW - MeDIP-seq

KW - Prostate cancer

KW - TRAMP

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U2 - https://doi.org/10.1186/s13578-018-0201-y

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