Epigenetics

2019 ◽  
pp. 239-268
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Air Pollution ◽  
Disease Risk ◽  
Environmental Pollutants ◽  
State Regulation ◽  
Metal Exposure ◽  
Environmental Toxicants ◽  
Water Chlorination ◽  
Epigenetic Patterns

This chapter focuses on epigenetics: the study of stable, often heritable changes that influence gene expression but are not mediated by DNA sequence. These changes play crucial roles in chromatin state regulation which influences processes such as gene expression, DNA repair, and recombination. Evidence demonstrates that epigenetic patterns are altered by environmental factors which are associated with disease risk including diet, smoking, alcohol intake, environmental toxicants, and stress. Studiers have linked environmental pollutants with epigenetic variations particularly changes in DNA methylation, histone modifications, and microRNAs. Growing data have linked epigenetic alterations with heavy metal exposure, organic toxicants, and water chlorination by-products. Studies focusing on the effects of air pollution in humans demonstrate an association between exposure to air pollution and DNA methylation. Several classes of pesticides can modify epigenetic marks, including endocrine disruptors, persistent organic pollutants, arsenic, several herbicides, and insecticides. This chapter explores epigenetics.

scholarly journals DNA methylation and gene expression integration in cardiovascular disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Guillermo Palou-Márquez ◽  
Isaac Subirana ◽  
Lara Nonell ◽  
Alba Fernández-Sanlés ◽  
Roberto Elosua
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Dna Methylation ◽  
Cardiovascular Diseases ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Risk Function ◽  
Predictive Biomarkers ◽  
Independent Study ◽  
Cell Type

Abstract Background The integration of different layers of omics information is an opportunity to tackle the complexity of cardiovascular diseases (CVD) and to identify new predictive biomarkers and potential therapeutic targets. Our aim was to integrate DNA methylation and gene expression data in an effort to identify biomarkers related to cardiovascular disease risk in a community-based population. We accessed data from the Framingham Offspring Study, a cohort study with data on DNA methylation (Infinium HumanMethylation450 BeadChip; Illumina) and gene expression (Human Exon 1.0 ST Array; Affymetrix). Using the MOFA2 R package, we integrated these data to identify biomarkers related to the risk of presenting a cardiovascular event. Results Four independent latent factors (9, 19, 21—only in women—and 27), driven by DNA methylation, were associated with cardiovascular disease independently of classical risk factors and cell-type counts. In a sensitivity analysis, we also identified factor 21 as associated with CVD in women. Factors 9, 21 and 27 were also associated with coronary heart disease risk. Moreover, in a replication effort in an independent study three of the genes included in factor 27 were also present in a factor identified to be associated with myocardial infarction (CDC42BPB, MAN2A2 and RPTOR). Factor 9 was related to age and cell-type proportions; factor 19 was related to age and B cells count; factor 21 pointed to human immunodeficiency virus infection-related pathways and inflammation; and factor 27 was related to lifestyle factors such as alcohol consumption, smoking and body mass index. Inclusion of factor 21 (only in women) improved the discriminative and reclassification capacity of the Framingham classical risk function and factor 27 improved its discrimination. Conclusions Unsupervised multi-omics data integration methods have the potential to provide insights into the pathogenesis of cardiovascular diseases. We identified four independent factors (one only in women) pointing to inflammation, endothelium homeostasis, visceral fat, cardiac remodeling and lifestyles as key players in the determination of cardiovascular risk. Moreover, two of these factors improved the predictive capacity of a classical risk function.

scholarly journals Early Pregnancy Exposure to Ambient Air Pollution among Late-Onset Preeclamptic Cases Is Associated with Placental DNA Hypomethylation of Specific Genes and Slower Placental Maturation

Toxics ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 338
Author(s):  
Karin Engström ◽  
Yumjirmaa Mandakh ◽  
Lana Garmire ◽  
Zahra Masoumi ◽  
Christina Isaxon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Air Pollution ◽  
Early Pregnancy ◽  
Late Onset ◽  
Dispersion Model ◽  
Ambient Air ◽  
Ambient Air Pollution ◽  
Dna Hypomethylation ◽  
Increased Risk

Exposure to ambient air pollution during pregnancy has been associated with an increased risk of preeclampsia (PE). Some suggested mechanisms behind this association are changes in placental DNA methylation and gene expression. The objective of this study was to identify how early pregnancy exposure to ambient nitrogen oxides (NOx) among PE cases and normotensive controls influence DNA methylation (EPIC array) and gene expression (RNA-seq). The study included placentas from 111 women (29 PE cases/82 controls) in Scania, Sweden. First-trimester NOx exposure was assessed at the participants’ residence using a dispersion model and categorized via median split into high or low NOx. Placental gestational epigenetic age was derived from the DNA methylation data. We identified six differentially methylated positions (DMPs, q < 0.05) comparing controls with low NOx vs. cases with high NOx and 14 DMPs comparing cases and controls with high NOx. Placentas with female fetuses showed more DMPs (N = 309) than male-derived placentas (N = 1). Placentas from PE cases with high NOx demonstrated gestational age deceleration compared to controls with low NOx (p = 0.034). No differentially expressed genes (DEGs, q < 0.05) were found. In conclusion, early pregnancy exposure to NOx affected placental DNA methylation in PE, resulting in placental immaturity and showing sexual dimorphism.

scholarly journals Epigenetics: Connecting Environment and Genotype to Phenotype and Disease

2009 ◽  
Vol 88 (5) ◽  
pp. 400-408 ◽  
Author(s):  
S.P. Barros ◽  
S. Offenbacher
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Expression Profiles ◽  
Chromatin Condensation ◽  
Methylation Status ◽  
Histone Deacetylation ◽  
Tissue Type ◽  
Cell Phenotype ◽  
Environment Interaction ◽  
Epigenetic Patterns

Genetic information is encoded not only by the linear sequence of DNA, but also by epigenetic modifications of chromatin structure that include DNA methylation and covalent modifications of the proteins that bind DNA. These “epigenetic marks” alter the structure of chromatin to influence gene expression. Methylation occurs naturally on cytosine bases at CpG sequences and is involved in controlling the correct expression of genes. DNA methylation is usually associated with triggering histone deacetylation, chromatin condensation, and gene silencing. Differentially methylated cytosines give rise to distinct patterns specific for each tissue type and disease state. Such methylation-variable positions (MVPs) are not uniformly distributed throughout our genome, but are concentrated among genes that regulate transcription, growth, metabolism, differentiation, and oncogenesis. Alterations in MVP methylation status create epigenetic patterns that appear to regulate gene expression profiles during cell differentiation, growth, and development, as well as in cancer. Environmental stressors including toxins, as well as microbial and viral exposures, can change epigenetic patterns and thereby effect changes in gene activation and cell phenotype. Since DNA methylation is often retained following cell division, altered MVP patterns in tissues can accumulate over time and can lead to persistent alterations in steady-state cellular metabolism, responses to stimuli, or the retention of an abnormal phenotype, reflecting a molecular consequence of gene-environment interaction. Hence, DNA epigenetics constitutes the main and previously missing link among genetics, disease, and the environment. The challenge in oral biology will be to understand the mechanisms that modify MVPs in oral tissues and to identify those epigenetic patterns that modify disease pathogenesis or responses to therapy.

scholarly journals Maternal environmental exposure to bisphenols and epigenome-wide DNA methylation in infant cord blood

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Carolyn F McCabe ◽  
Vasantha Padmanabhan ◽  
Dana C Dolinoy ◽  
Steven E Domino ◽  
Tamara R Jones ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cord Blood ◽  
Disease Risk ◽  
Estimation Algorithm ◽  
First Trimester ◽  
Type I ◽  
Environmental Toxicants ◽  
Cell Type ◽  
Bisphenol S ◽  
Blood Leukocytes

Abstract Maternal prenatal exposures, including bisphenol A (BPA), are associated with offspring’s risk of disease later in life. Alterations in DNA methylation may be a mechanism through which altered prenatal conditions (e.g. maternal exposure to environmental toxicants) elicit this disease risk. In the Michigan Mother and Infant Pairs Cohort, maternal first-trimester urinary BPA, bisphenol F, and bisphenol S concentrations were tested for association with DNA methylation patterns in infant umbilical cord blood leukocytes (N = 69). We used the Illumina Infinium MethylationEPIC BeadChip to quantitatively evaluate DNA methylation across the epigenome; 822 020 probes passed pre-processing and quality checks. Single-site DNA methylation and bisphenol models were adjusted for infant sex, estimated cell-type proportions (determined using cell-type estimation algorithm), and batch as covariates. Thirty-eight CpG sites [false discovery rate (FDR) &lt;0.05] were significantly associated with maternal BPA exposure. Increasing BPA concentrations were associated with lower DNA methylation at 87% of significant sites. BPA exposure associated DNA methylation sites were enriched for 38 pathways significant at FDR &lt;0.05. The pathway or gene-set with the greatest odds of enrichment for differential methylation (FDR &lt;0.05) was type I interferon receptor binding. This study provides a novel understanding of fetal response to maternal bisphenol exposure through epigenetic change.

scholarly journals Integrative genomic strategies applied to a lymphoblast cell line model reveal specific transcriptomic signatures associated with clozapine response

2020 ◽  
Author(s):  
SAJ de With ◽  
APS Ori ◽  
T Wang ◽  
SL Pulit ◽  
E Strengman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Adverse Effects ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Disease Risk ◽  
Density Lipoprotein ◽  
Expression Levels ◽  
Genome Wide ◽  
Gene Expression Levels

AbstractClozapine is an important antipsychotic drug. However, its use is often accompanied by metabolic adverse effects and, in rare instances, agranulocytosis. The molecular mechanisms underlying these adverse events are unclear. To gain more insights into the response to clozapine at the molecular level, we exposed lymphoblastoid cell lines (LCLs) to increasing concentrations of clozapine and measured genome-wide gene expression and DNA methylation profiles. We observed robust and significant changes in gene expression levels due to clozapine (n = 463 genes at FDR < 0.05) affecting cholesterol and cell cycle pathways. At the level of DNA methylation, we find significant changes upstream of the LDL receptor, in addition to global enrichments of regulatory, immune and developmental pathways. By integrating these data with human tissue gene expression levels obtained from the Genotype-Tissue Expression project (GTEx), we identified specific tissues, including liver and several tissues involved in immune, endocrine and metabolic functions, that clozapine treatment may disproportionately affect. Notably, differentially expressed genes were not enriched for genome-wide disease risk of schizophrenia or for known psychotropic drug targets. However, we did observe a nominally significant association of genetic signals related to total cholesterol and low-density lipoprotein levels. Together, these results shed light on the biological mechanisms through which clozapine functions. The observed associations with cholesterol pathways, its genetic architecture and specific tissue effects may be indicative of the metabolic adverse effects observed in clozapine users. LCLs may thus serve as a useful tool to study these molecular mechanisms further.

Maternal diet as a modifier of offspring epigenetics

2015 ◽  
Vol 6 (2) ◽  
pp. 88-95 ◽  
Author(s):  
K. A. Lillycrop ◽  
G. C. Burdge
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Early Life ◽  
Disease Risk ◽  
Important Determinant ◽  
Maternal Diet ◽  
Substantial Body ◽  
Highly Sensitive ◽  
Non Coding Rnas ◽  
Epigenetic Processes

There has been a substantial body of evidence, which has shown that genetic variation is an important determinant of disease risk. However, there is now increasing evidence that alterations in epigenetic processes also play a role in determining susceptibility to disease. Epigenetic processes, which include DNA methylation, histone modifications and non-coding RNAs play a central role in regulating gene expression, determining when and where a gene is expressed as well as the level of gene expression. The epigenome is highly sensitive to a variety of environmental factors, especially in early life. One factor that has been shown consistently to alter the epigenome is maternal diet. This review will focus on how maternal diet can modify the epigenome of the offspring, producing different phenotypes and altered disease susceptibilities.

scholarly journals Environmental Exposure to Endocrine Disrupting Chemicals Influences Genomic Imprinting, Growth, and Metabolism

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1153
Author(s):  
Nicole Robles-Matos ◽  
Tre Artis ◽  
Rebecca A. Simmons ◽  
Marisa S. Bartolomei
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Early Development ◽  
Genomic Imprinting ◽  
Disease Risk ◽  
Expression Patterns ◽  
Endocrine Disrupting Chemicals ◽  
Epigenetic Mechanism ◽  
Increased Risk ◽  
Endocrine Disrupting

Genomic imprinting is an epigenetic mechanism that results in monoallelic, parent-of-origin-specific expression of a small number of genes. Imprinted genes play a crucial role in mammalian development as their dysregulation result in an increased risk of human diseases. DNA methylation, which undergoes dynamic changes early in development, is one of the epigenetic marks regulating imprinted gene expression patterns during early development. Thus, environmental insults, including endocrine disrupting chemicals during critical periods of fetal development, can alter DNA methylation patterns, leading to inappropriate developmental gene expression and disease risk. Here, we summarize the current literature on the impacts of in utero exposure to endocrine disrupting chemicals on genomic imprinting and metabolism in humans and rodents. We evaluate how early-life environmental exposures are a potential risk factor for adult metabolic diseases. We also introduce our mouse model of phthalate exposure. Finally, we describe the potential of genomic imprinting to serve as an environmental sensor during early development and as a novel biomarker for postnatal health outcomes.

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