Emerging Concept in DNA Methylation: Role of Transcription Factors in Shaping DNA Methylation Patterns

Marchal, Claire; Miotto, Benoît

doi:10.1002/jcp.24836

Cited by 64 publications

(53 citation statements)

References 97 publications

(198 reference statements)

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“…Eighth, there is potential for selection bias if participation in the study was influenced by proximity to major roadway conditional on the demographic and socioeconomic factors included in our models. Finally, the observed epigenetic changes may not represent changes in gene expression, which depend on the CpG site's location on the genome and the promoter's CpG density (Marchal and Miotto 2015). However, DNA methylation reset early in development and is critical in in defining tissue differentiation and function.…”

Section: 0 Discussionmentioning

confidence: 99%

Maternal residential proximity to major roadways, birth weight, and placental DNA methylation

Kingsley

Eliot

Whitsel

et al. 2016

Environment International

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Background Exposure to traffic pollution during fetal development has been associated with reduced fetal growth, and there is evidence to suggest that epigenetic mechanisms in the placenta in the form of variant DNA methylation may be a potential mechanism of this effect. Objectives To examine the association between residential proximity to nearest major roadway, as a marker of traffic-related pollution, fetal growth and placental DNA methylation. Methods We obtained residential addresses, placenta samples, and demographic data from 471 women following delivery. Using generalized linear models we evaluated the association between living close to a major roadway (defined as living ≤150 m from a primary highway or primary road or ≤50 m from a secondary road) and fetal growth and DNA methylation of repetitive elements (LINE-1 and AluYb8). We evaluated epigenome-wide methylation in a subset of 215 women to further investigate specific variation in DNA methylation associated with proximity to major roadways. Results Living close to a major roadway was associated with a 175.9 g (95% CI: -319.4, -32.5; p=0.016) lower birth weight, 1.8 (95% CI: 0.9, 3.8; p=0.09) times the odds of being small for gestational age, and 0.82 percentage points (95% CI: −1.57, −0.07; p=0.03) lower mean placental LINE-1 methylation levels in fully adjusted models. In epigenome-wide analyses, 7 CpG sites were significantly associated with residential proximity to major roadways. Additional adjustment for placental methylation did not attenuate the association between roadway proximity and birth weight. Conclusions Living close to major roadways was associated with lower fetal growth and significant placental epigenetic changes. However, the observed epigenetic changes appear insufficient to explain the observed association between roadway proximity and fetal growth.

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Section: 0 Discussionmentioning

confidence: 99%

Maternal residential proximity to major roadways, birth weight, and placental DNA methylation

Kingsley

Eliot

Whitsel

et al. 2016

Environment International

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“…As reverse correlations between DNA methylation and gene expression were seen in psoriatic epidermis and tongue SCC, and transcription factors could be important drivers of methylation changes534, it seems likely that under distinct pathological conditions, different transcriptional factors targeting different genomic elements are recruited for activating OAS2 expression. The general hypomethylation of OAS2 seen in psoriasis might functionally be related to OAS2 mRNA up-regulation, whereas in SCC of the mobile tongue, local decreased methylation at only two CpG sites (CpG2 and 3) seems sufficient to affect regulation of OAS2 expression.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic regulation of OAS2 shows disease-specific DNA methylation profiles at individual CpG sites

Boldrup

Coates

et al. 2016

Sci Rep

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Epigenetic modifications are essential regulators of biological processes. Decreased DNA methylation of OAS2 (2′-5′-Oligoadenylate Synthetase 2), encoding an antiviral protein, has been seen in psoriasis. To provide further insight into the epigenetic regulation of OAS2, we performed pyrosequencing to detect OAS2 DNA methylation status at 11 promoter and first exon located CpG sites in psoriasis (n = 12) and two common subtypes of squamous cell carcinoma (SCC) of the head and neck: tongue (n = 12) and tonsillar (n = 11). Compared to corresponding controls, a general hypomethylation was seen in psoriasis. In tongue and tonsillar SCC, hypomethylation was found at only two CpG sites, the same two sites that were least demethylated in psoriasis. Despite differences in the specific residues targeted for methylation/demethylation, OAS2 expression was upregulated in all conditions and correlations between methylation and expression were seen in psoriasis and tongue SCC. Distinctive methylation status at four successively located CpG sites within a genomic area of 63 bp reveals a delicately integrated epigenetic program and indicates that detailed analysis of individual CpGs provides additional information into the mechanisms of epigenetic regulation in specific disease states. Methylation analyses as clinical biomarkers need to be tailored according to disease-specific sites.

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“…This is achieved by interaction with repressor proteins, chromatin remodeling enzymes, methyltransferases, and also small non-coding RNAs to open the chromatin and allow for remodeling, leading to either activation or repression of transcriptional activity (Marchal and Miotto, 2015;Meaney and Ferguson-Smith, 2010).…”

Section: Activation Of Transcription Factors That Lead To Local Changmentioning

confidence: 99%

Epigenetics of Stress-Related Psychiatric Disorders and Gene × Environment Interactions

Klengel

Binder

2015

Neuron

294

184

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A deeper understanding of the pathomechanisms leading to stress-related psychiatric disorders is important for the development of more efficient preventive and therapeutic strategies. Epidemiological studies indicate a combined contribution of genetic and environmental factors in the risk for disease. The environment, particularly early life severe stress or trauma, can lead to lifelong molecular changes in the form of epigenetic modifications that can set the organism off on trajectories to health or disease. Epigenetic modifications are capable of shaping and storing the molecular response of a cell to its environment as a function of genetic predisposition. This provides a potential mechanism for gene-environment interactions. Here, we review epigenetic mechanisms associated with the response to stress and trauma exposure and the development of stress-related psychiatric disorders. We also look at how they may contribute to our understanding of the combined effects of genetic and environmental factors in shaping disease risk.

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Emerging Concept in DNA Methylation: Role of Transcription Factors in Shaping DNA Methylation Patterns

Cited by 64 publications

References 97 publications

Maternal residential proximity to major roadways, birth weight, and placental DNA methylation

Maternal residential proximity to major roadways, birth weight, and placental DNA methylation

Epigenetic regulation of OAS2 shows disease-specific DNA methylation profiles at individual CpG sites

Epigenetics of Stress-Related Psychiatric Disorders and Gene × Environment Interactions

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