Widespread and tissue specific age-related DNA methylation changes in mice

Shinji Maegawa, George Hinkal, Hyun Soo Kim, Lanlan Shen, Li Zhang, Jiexin Zhang, Nianxiang Zhang, Shoudan Liang, Lawrence A. Donehower, Jean Pierre J. Issa

Research output: Contribution to journalArticle

318 Citations (Scopus)

Abstract

Aberrant methylation of promoter CpG islands in cancer is associated with silencing of tumor-suppressor genes, and agedependent hypermethylation in normal appearing mucosa may be a risk factor for human colon cancer. It is not known whether this age-related DNA methylation phenomenon is specific to human tissues. We performed comprehensive DNA methylation profiling of promoter regions in aging mouse intestine using methylated CpG island amplification in combination with microarray analysis. By comparing C57BL/6 mice at 3-mo-old versus 35-mo-old for 3627 detectable autosomal genes, we found 774 (21%) that showed increased methylation and 466 (13%) that showed decreased methylation. We used pyrosequencing to quantitatively validate the microarray data and confirmed linear age-related methylation changes for all 12 genomic regions examined. We then examined 11 changed genomic loci for age-related methylation in other tissues. Of these, three of 11 showed similar changes in lung, seven of 11 changed in liver, and six of 11 changed in spleen, though to a lower degree than the changes seen in colon. There was partial conservation between agerelated hypermethylation in human and mouse intestines, and Polycomb targets in embryonic stem cells were enriched among the hypermethylated genes. Our findings demonstrate a surprisingly high rate of hyper- and hypomethylation as a function of age in normal mouse small intestine tissues and a strong tissue-specificity to the process. We conclude that epigenetic deregulation is a common feature of aging in mammals.

Original languageEnglish
Pages (from-to)332-340
Number of pages9
JournalGenome Research
Volume20
Issue number3
DOIs
Publication statusPublished - 2010 Mar 1

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DNA Methylation
Methylation
CpG Islands
Intestines
Organ Specificity
DNA Fingerprinting
Microarray Analysis
Embryonic Stem Cells
Tumor Suppressor Genes
Inbred C57BL Mouse
Genetic Promoter Regions
Epigenomics
Colonic Neoplasms
Genes
Small Intestine
Mammals
Colon
Mucous Membrane
Spleen
Lung

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Maegawa, S., Hinkal, G., Kim, H. S., Shen, L., Zhang, L., Zhang, J., ... Issa, J. P. J. (2010). Widespread and tissue specific age-related DNA methylation changes in mice. Genome Research, 20(3), 332-340. https://doi.org/10.1101/gr.096826.109
Maegawa, Shinji ; Hinkal, George ; Kim, Hyun Soo ; Shen, Lanlan ; Zhang, Li ; Zhang, Jiexin ; Zhang, Nianxiang ; Liang, Shoudan ; Donehower, Lawrence A. ; Issa, Jean Pierre J. / Widespread and tissue specific age-related DNA methylation changes in mice. In: Genome Research. 2010 ; Vol. 20, No. 3. pp. 332-340.
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Maegawa, S, Hinkal, G, Kim, HS, Shen, L, Zhang, L, Zhang, J, Zhang, N, Liang, S, Donehower, LA & Issa, JPJ 2010, 'Widespread and tissue specific age-related DNA methylation changes in mice', Genome Research, vol. 20, no. 3, pp. 332-340. https://doi.org/10.1101/gr.096826.109

Widespread and tissue specific age-related DNA methylation changes in mice. / Maegawa, Shinji; Hinkal, George; Kim, Hyun Soo; Shen, Lanlan; Zhang, Li; Zhang, Jiexin; Zhang, Nianxiang; Liang, Shoudan; Donehower, Lawrence A.; Issa, Jean Pierre J.

In: Genome Research, Vol. 20, No. 3, 01.03.2010, p. 332-340.

Research output: Contribution to journalArticle

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