A Minimal Set of Tissue-Specific Hypomethylated CpGs Constitute Epigenetic Signatures of Developmental Programming

Colaneri, Alejandro; Wang, Tianyuan; Pagadala, Vijayakanth; Kittur, Jaya; Staffa, Nickolas G.; Peddada, Shyamal D.; Isganaitis, Elvira; Patti, Mary Elizabeth; Birnbaumer, Lutz

doi:10.1371/journal.pone.0072670

Cited by 17 publications

(11 citation statements)

References 56 publications

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“…These results are reinforced by those obtained from the comparison of the distribution of methylation levels between VAT and blood, showing a higher number of highly methylated CpG sites in blood and with known tissue-specific gene expression. High proportions of differentially methylated sites located in intergenic and gene body regions reported here are consistent with results from mice [38] and humans [31,39] suggesting a role for intragenic and intergenic CpG site methylation in tissue-specific gene expression. Taken as a whole, higher intra-than inter-tissue correlation reported here and in other studies, clustering and PCA analyses, as well as differences in methylation levels between VAT and blood add to the evidence for tissue-specific methylation patterns [26,31,38,40].…”

Section: Discussionsupporting

confidence: 89%

Use of Blood as a Surrogate Model for the Assessment of Visceral Adipose Tissue Methylation Profiles Associated with the Metabolic Syndrome in Men

Guénard¹,

Deshaies²,

Hould³

et al. 2016

J Mol Genet Med

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Epigenetic mechanisms are known to be involved in tissue-specific differentiation. DNA methylation patterns have been shown to be largely conserved across tissues but with variation for specific genes. However, it is unclear whether the variability observed in the methylation profile of a metabolically active tissue is reflected in other sources such as hematopoietic tissue. This study aimed to test blood genome-wide CpG site methylation levels as a surrogate model for visceral adipose tissue (VAT) methylation and to verify whether it appropriately reflects differences in methylation levels found in VAT between men discordant for the metabolic syndrome (MetS). Tissue specimens (VAT and blood samples) were obtained from 16 severely obese individuals discordant for the MetS. CpG sites methylation levels were measured with the Infinium HumanMethylation450 BeadChip and correlations of methylation levels between VAT and blood were computed. Differences in methylation levels between individuals with and without MetS were tested in both tissues. Pathway analysis was conducted for differentially methylated CpG sites common to both tissues. High cross-tissue correlations were observed for VAT and blood (0.952±0.014) while some CpG sites had significantly different methylation levels in VAT versus blood. Differential methylation analysis between individuals with and without MetS demonstrated a higher number of differentially methylated CpG sites in VAT than in blood (11,778 vs. 881, respectively) with nearly 4% of differentially methylated sites found in VAT being also represented in blood. Common differentially methylated sites were involved in inflammatory-, lipid-and diabetes-related pathways. These results suggest that blood methylation levels of specific CpG sites may adequately reflect VAT methylation levels for some of the MetS-related genes, specifically for inflammatory, lipid and glucose metabolism genes.

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Section: Discussionsupporting

confidence: 89%

Use of Blood as a Surrogate Model for the Assessment of Visceral Adipose Tissue Methylation Profiles Associated with the Metabolic Syndrome in Men

Guénard¹,

Deshaies²,

Hould³

et al. 2016

J Mol Genet Med

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“…In this study, the occurrence rate of PAX5 promoter methylation (78.48%) in the 460 GC patients was similar to the finding of previous study [ 8 ]. Many researchers proposed that the methylated CpG site detection was appropriate for precisely quantitative evaluation the correlation between the methylated levels of gene promoter and the various abnormally biological events [ 15 - 18 ]. Subsequently, we meticulously analyzed the methylated CpG sites of PAX5 promoter in 460 GC patients by using the BGS method with no less than five positive clones for each GC sample.…”

Section: Discussionmentioning

confidence: 99%

Applicability of the methylated CpG sites of paired box 5 (PAX5) promoter for prediction the prognosis of gastric cancer

et al. 2014

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Paired box gene 5 (PAX5), a member of the paired box gene family, is involved in control of organ development and tissue differentiation. In previous study, PAX5 promoter methylation was found in gastric cancer (GC) cells and tissues. At present study, we found that the inconsistently methylated levels of PAX5 promoter were identified in the different GC tissues. The methylated CpG site count and the methylated statuses of four CpG sites (-236, -183, -162, and -152) were significantly associated with the survival of 460 GC patients, respectively. Ultimately, the methylated CpG -236 was the optimal prognostic predictor of patients identified by using the Cox regression with AIC value calculation. These findings indicated that the methylated CpG -236 of PAX5 promoter has the potential applicability for clinical evaluation the prognosis of GC.

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“…Indeed, supplementation or restriction of the maternal diet with dietary factors can alter epigenetic patterns in offspring 21, 22 . A large number of tissue-specific differentially methylated sites were observed in livers of mice exposed to nutritional stress during development 23 . Similarly, epigenetic alterations were observed in the prostate after neonatal exposure to bisphenol A 24 .…”

Section: Mechanistic Understanding Of How Developmental Environmentalmentioning

confidence: 99%

Developmental origins of health and disease

Heindel

Vandenberg

2015

Current Opinion in Pediatrics

307

108

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Purpose of Review While diseases may appear clinically throughout the lifespan, it is clear that many diseases have origins during development. Altered nutrition, as well as exposure to environmental chemicals, drugs, infections, or stress during specific times of development can lead to functional changes in tissues, predisposing those tissues to diseases that manifest later in life. This review will focus on the role of altered nutrition and exposures to environmental chemicals during development in the role of disease/dysfunctions. Recent Findings Effects of altered nutrition or exposure to environmental chemicals during development are likely due to altered programming of epigenetic marks which persist across the lifespan. Indeed some changes can be transmitted to future generations. Summary Evidence in support of the DOHaD paradigm is sufficiently robust and repeatable across species including humans, suggesting a need for greater emphasis in the clinical area. Because of these data, obesity, diabetes, cardiovascular morbidity, and neuropsychiatric diseases can all be considered pediatric diseases. Disease prevention must start with improved nutrition and reduced exposures to environmental chemicals during development.

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A Minimal Set of Tissue-Specific Hypomethylated CpGs Constitute Epigenetic Signatures of Developmental Programming

Cited by 17 publications

References 56 publications

Use of Blood as a Surrogate Model for the Assessment of Visceral Adipose Tissue Methylation Profiles Associated with the Metabolic Syndrome in Men

Use of Blood as a Surrogate Model for the Assessment of Visceral Adipose Tissue Methylation Profiles Associated with the Metabolic Syndrome in Men

Applicability of the methylated CpG sites of paired box 5 (PAX5) promoter for prediction the prognosis of gastric cancer

Developmental origins of health and disease

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