Alterations of c-fos gene methylation in the processes of aging and tumorigenesis in human liver

Choi, Eunji; Uyeno, Shinji; Nishida, Naoshi; Okumoto, Tadayuki; Fujimura, Shigefumi; Aoki, Yasuhiro; Nata, Masayuki; Sagisaka, Kaoru; Fukuda, Yoshihiro; Nakao, Kazuwa; Yoshimoto, Takashi; Kim, Y.S.; Ono, Tetsuya

doi:10.1016/0027-5107(96)00056-5

Cited by 41 publications

(18 citation statements)

References 17 publications

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“…A number of human tissue studies have reported associations between cross-sectional age and gene-specific DNA methylation. Hypermethylation of a number of specific genes has been associated with cross-sectional age including the estrogen receptor (ER) (human colonic mucosa), 17 22 and collagen α1 (periodontal ligament tissue). 23 In addition, genes associated with colorectal cancer, including MYOD and N33, have been associated with age-related partial methylation in normal colon mucosa.…”

Section: Discussionmentioning

confidence: 99%

Aging and epigenetics: Longitudinal changes in gene-specific DNA methylation

et al. 2012

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Section: Discussionmentioning

confidence: 99%

Aging and epigenetics: Longitudinal changes in gene-specific DNA methylation

et al. 2012

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“…The successful identification of differentially methylated regions (DMRs) associated with aging in studies of candidate loci (12)(13)(14) has stimulated interest in mapping all such sites * To whom correspondence should be addressed at: Center for Biomarker Research and Personalized Medicine, McGuire Hall, Medical College of Virginia campus, Virginia Commonwealth University, 1112 East Clay Street, Richmond, VA 23298, USA. Tel: +1 8048283428; Fax: +1 8046283991; Email: jlmcclay@vcu.edu genome-wide.…”

Section: Introductionmentioning

confidence: 99%

A methylome-wide study of aging using massively parallel sequencing of the methyl-CpG-enriched genomic fraction from blood in over 700 subjects

McClay¹,

Åberg²,

Clark³

et al. 2013

Human Molecular Genetics

150

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The central importance of epigenetics to the aging process is increasingly being recognized. Here we perform a methylome-wide association study (MWAS) of aging in whole blood DNA from 718 individuals, aged 25 -92 years (mean 5 55). We sequenced the methyl-CpG-enriched genomic DNA fraction, averaging 67.3 million reads per subject, to obtain methylation measurements for the ∼27 million autosomal CpGs in the human genome. Following extensive quality control, we adaptively combined methylation measures for neighboring, highly-correlated CpGs into 4 344 016 CpG blocks with which we performed association testing. Eleven age-associated differentially methylated regions (DMRs) passed Bonferroni correction (P-value < 1.15 3 10 28 ). Top findings replicated in an independent sample set of 558 subjects using pyrosequencing of bisulfite-converted DNA (min P-value < 10 230 ). To examine biological themes, we selected 70 DMRs with false discovery rate of <0.1. Of these, 42 showed hypomethylation and 28 showed hypermethylation with age. Hypermethylated DMRs were more likely to overlap with CpG islands and shores. Hypomethylated DMRs were more likely to be in regions associated with polycomb/regulatory proteins (e.g. EZH2) or histone modifications H3K27ac, H3K4m1, H3K4m2, H3K4m3 and H3K9ac. Among genes implicated by the top DMRs were protocadherins, homeobox genes, MAPKs and ryanodine receptors. Several of our DMRs are at genes with potential relevance for age-related disease. This study successfully demonstrates the application of next-generation sequencing to MWAS, by interrogating a large proportion of the methylome and returning potentially novel age DMRs, in addition to replicating several loci implicated in previous studies using microarrays.

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“…Such age-related progressive methylation has been reported in the CpG islands of a few candidate tumour suppressor genes ± Estrogen receptor (Issa et al, 1994), N33 Ahuja et al, 1998), an imprinted IGF2 and a proto-oncogene c-fos (Choi et al, 1996). In colorectal mucosal cells, age-related methylation seems to be both gene-speci®c and tissue-speci®c .…”

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confidence: 98%

Hypermethylation at 9q32-33 tumour suppressor region is age-related in normal urothelium and an early and frequent alteration in bladder cancer

et al. 2001

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Transcriptional silencing by CpG island hypermethylation of gene regulatory regions is one mechanism for inactivation of tumour suppressor genes. Chromosome 9q deletion is frequently found in transitional cell carcinoma (TCC) of the bladder and upper urinary tract and one of the putative tumour suppressor loci has been mapped to 9q32-33. A gene designated as DBCCR1 was identi®ed in the candidate region and its mRNA expression is thought to be suppressed by hypermethylation. To understand the role of hypermethylation in TCC, we evaluated the methylation status of 20 CpG sites of the DBCCR1 5'-CpG island region in a total of 69 tumours from 45 patients, 21 normal urothelial specimens, and six bladder cancer cell lines. Aberrant hypermethylation levels were found in 36 (52%) of 69 tumours without any association with tumour grade or stage. Methylation was weakly detected in the normal urothelium in association with ageing. Although recurrent tumours tended to have higher methylation levels than the initial tumours, the methylation pattern was mostly maintained between multifocal TCCs in individual patients. The results suggest that hypermethylation of the DBCCR1 region is one of the earliest alterations in the development of TCCs and there may be an age-related hypermethylation-based ®eld defect in normal urothelium. Methylator or methylation-resistant phenotype seems to be maintained during multifocal development or recurrence of most TCCs. Oncogene (2001) 20, 531 ± 537.

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Alterations of c-fos gene methylation in the processes of aging and tumorigenesis in human liver

Cited by 41 publications

References 17 publications

Aging and epigenetics: Longitudinal changes in gene-specific DNA methylation

Aging and epigenetics: Longitudinal changes in gene-specific DNA methylation

A methylome-wide study of aging using massively parallel sequencing of the methyl-CpG-enriched genomic fraction from blood in over 700 subjects

Hypermethylation at 9q32-33 tumour suppressor region is age-related in normal urothelium and an early and frequent alteration in bladder cancer

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