DNA methylation profiling of human chromosomes 6, 20 and 22

Eckhardt, Florian; Lewin, Joern; Cortese, Rene; Rakyan, Vardhman K.; Attwood, J.; Burger, Matthias; Burton, John H.; Cox, Tony; Davies, Rob; Down, Thomas A.; Haefliger, Carolina; Horton, Roger W.; Howe, Kevin; Jackson, David; Kunde, Jan; Koenig, Christoph; Liddle, Jennifer; Niblett, David; Otto, Thomas; Pettett, Roger; Seemann, Stefanie; Thompson, Christian; West, Tony; Rogers, Jane; Olek, Alex; Berlin, Kurt; Beck, Stephan

doi:10.1038/ng1909

Cited by 1,223 publications

(1,136 citation statements)

References 47 publications

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“…In many of these conditions TNF acts as a pivotal mediator of inflammation and tissue damage; our data suggests that age-related DNA TNF promoter demethylation could contribute to the late peak in incidence of these conditions [27]. The relationship between gender and methylation status is controversial; lower genomic levels have been reported in peripheral blood white cells of healthy females [28], however another study examined mean methylation in a range of organs and primary cell types did not detect significant gender-related differences [19]. Levels of DNA methylation are lower in peripheral blood T cells from patients with either rheumatoid arthritis or systemic lupus erythematosus compared with healthy controls [29], both of which occur more frequently in females, although whether this is a primary abnormality or is secondary to the disease or its treatment is not known.…”

Section: Discussionmentioning

confidence: 59%

“…Although recent studies have challenged the belief that global DNA methylation decreases with age [18,19], recent evidence suggests that immune genes may be particularly prone to age-related change in DNA methylation [18]. The expression of killer Ig-like receptors on T cells is known to increase with age and KIR2DL4 promoter methylation is lower in T cells isolated from 70-80 year old donors compared with those from 20-40 year old individuals [20].…”

Section: Introductionmentioning

confidence: 99%

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Age-related loss of CpG methylation in the tumour necrosis factor promoter

et al. 2011

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Background: Dysregulated production of TNF has been implicated in the pathogenesis and severity of inflammatory rheumatic diseases, many of which show age-related increased incidence. Ageing is also associated with changes in the immune system including higher systemic levels of pro-inflammatory cytokines.Methylation of DNA is an important regulator of gene expression and changes with age.Objective: In this study we investigated whether the DNA methylation status of the TNF promoter changed with age in peripheral blood leukocytes and macrophages. Methods and results:Using pyrosequencing assays we detected age-related demethylation of CpG motifs (-304, -245 and -239) Conclusions: These data suggest a potential role of accrued changes in DNA methylation in the development of age-related inflammatory diseases, such as rheumatoid arthritis and polymyalgia rheumatica, in which TNF is a pivotal mediator.3

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Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Age-related loss of CpG methylation in the tumour necrosis factor promoter

et al. 2011

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“…accumulated DNA damage) is not clear, but it is feasible that epigenetics accounts for at least part of the change. Underscoring this possibility, age-associated divergence of DNA methylation and histone acetylation profiles has been found in pairs of monozygous twins that are genetically identical [107] (but see also ref [108]). Remarkably, in the twin study, those genes that were differentially modified were also differentially expressed, suggesting that age-associated epigenetic divergence drives age-associated divergence of gene expression profiles.…”

Section: The Consequences Of Age-associated Epigenetic Changesmentioning

confidence: 99%

Aging by epigenetics—A consequence of chromatin damage?

Sedivy

Gowrishankar

Adams

2008

Experimental Cell Research

140

102

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Chromatin structure is not fixed. Instead, chromatin is dynamic and is subject to extensive developmental and age-associated remodeling. In some cases, this remodeling appears to counter the aging and age-associated diseases, such as cancer, and extend organismal lifespan. However, stochastic non-deterministic changes in chromatin structure might, over time, also contribute to the break down of nuclear, cell and tissue function, and consequently aging and age-associated diseases.

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“…It is assumed that DNA methylation of specific sites, particularly in the promoter region, may suppress the expression of the gene [43,44]. Although the expression of COX7A1 is tissue-specific, this gene is located in a CpG island, a feature which is commonly seen among housekeeping genes [6].…”

mentioning

confidence: 99%

Age influences DNA methylation and gene expression of COX7A1 in human skeletal muscle

et al. 2008

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Aims/hypothesis Reduced oxidative capacity of the mitochondria in skeletal muscle has been suggested to contribute to insulin resistance and type 2 diabetes. Moreover, a set of genes influencing oxidative phosphorylation (OXPHOS) is downregulated in diabetic muscle. Here we studied whether genetic, epigenetic and non-genetic factors influence a component of the respiratory chain, COX7A1, previously shown to be downregulated in skeletal muscle from patients with type 2 diabetes. The specific aims were to: (1) evaluate the impact of genetic (single nucleotide polymorphisms [SNPs]), epigenetic (DNA methylation) and non-genetic (age) factors on the expression of COX7A1 in human skeletal muscle; and (2) investigate whether common variants in the COX7A1 gene are associated with increased risk of type 2 diabetes. Methods COX7A1 mRNA expression was analysed in muscle biopsies from young (n=110) and elderly (n=86) non-diabetic twins and related to measures of in vivo metabolism. Genetic variants (three SNPs) from the COX7A1 locus were genotyped in the twins and in two independent type 2 diabetes case-control cohorts (n=1466 and 6380, respectively). DNA methylation of the COX7A1 promoter was analysed in a subset of twins (ten young, ten elderly) using bisulphite sequencing. Results While DNA methylation of the COX7A1 promoter was increased in muscle from elderly compared with young twins (19.9±8.3% vs 1.8±2.7%; p=0.035), the opposite was found for COX7A1 mRNA expression (elderly 1.00±0.05 vs young 1.68 ± 0.06; p = 0.0005). The heritability of COX7A1 expression was estimated to be 50% in young and 72% in elderly twins. One of the polymorphisms investigated, rs753420, influenced basal COX7A1 expression in muscle of young (p=0.0001) but not of elderly twins. The transcript level of COX7A1 was associated with increased in vivo glucose uptake and V : O 2max (p=0.009 and p=0.001, respectively). We did not observe any genetic association between COX7A1 polymorphisms and type 2 diabetes after correcting for multiple testing. Diabetologia (2008) Conclusions/interpretation Our results provide further evidence for age as a factor influencing DNA methylation and expression of OXPHOS genes, and thereby in vivo metabolism.

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DNA methylation profiling of human chromosomes 6, 20 and 22

Cited by 1,223 publications

References 47 publications

Age-related loss of CpG methylation in the tumour necrosis factor promoter

Age-related loss of CpG methylation in the tumour necrosis factor promoter

Aging by epigenetics—A consequence of chromatin damage?

Age influences DNA methylation and gene expression of COX7A1 in human skeletal muscle

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