How Pollutants Affect Dna Methylation And Gene Expression

DNA methylation is an epigenetic modulator that is influenced by environmental stimuli, including exposure to pollutants. DNA methylation involves the addition of a methyl group to the DNA molecule, which can affect gene expression and subsequent protein expression. While DNA methylation is necessary for normal development and differentiation, it is also susceptible to modulation by environmental factors such as diet, hormones, stress, drugs, and exposure to pollutants. Studies have shown that exposure to air pollution, heavy metals, and persistent organic pollutants can lead to alterations in DNA methylation patterns, which may have adverse health outcomes. However, the specific mechanisms underlying these associations are not yet fully understood, and more research is needed to determine the extent and specificity of these effects.

DNA methylation and air pollution

DNA methylation is a reversible biological signal that is the most extensively studied epigenetic modulator in response to environmental stimuli. It involves the addition of a methyl group (-CH2) to the fifth carbon position of the cytosine base, a process facilitated by DNA methyltransferases (DNMTs) enzymes. This modification can influence gene expression and subsequent protein expression without altering the primary DNA sequence.

Several studies have indicated that DNA methylation patterns can be influenced by environmental factors like air pollution, and these epigenetic changes are linked to diverse diseases. Air pollution exposure is estimated to contribute to approximately seven million early deaths annually worldwide and over 3% of disability-adjusted life years lost. It has been associated with numerous harmful health effects, including oxidative stress, cardiovascular diseases, metabolic disorders, respiratory diseases, and cancer.

Traffic-related air pollution (TRAP) is a major source of urban air pollution and has been linked to various diseases, including cardiovascular and metabolic diseases. TRAP exposure has been associated with methylation changes in 68 CpG loci, with 49 hypermethylated and 19 hypomethylated. These annotated genes are related to pathways in cardiovascular signalling, cytokine signalling, immune response, nervous system signalling, and metabolism.

Studies have also examined the impact of specific air pollutants on DNA methylation. For example, exposure to black carbon, a component of TRAP, has been associated with significantly higher DNA methylation in nasal brushings at cg23602092 in the promoter region of TET1. O3 exposure during the first trimester was associated with increased systolic blood pressure in 11-year-old children with particular DNMT1 or DNMT3B isoforms. Exposure to nitrogen dioxide (NO2), another component of TRAP, during pregnancy has been linked to DNA methylation at three CpGs in cord blood samples.

Overall, air pollution-induced reactive oxygen species (ROS) may increase oxidation and influence the balance of cytosine (C) and 5-methylcytosine (5-mC) at CpGs throughout the genome. While the specific mechanisms remain to be fully elucidated, the available evidence suggests that air pollution exposure can lead to DNA methylation changes, which may contribute to the development and exacerbation of various diseases.

DNA methylation and autism spectrum disorders

DNA methylation is the most extensively studied epigenetic modulator in response to environmental stimuli. It involves the addition of a methyl group (-CH2) to the fifth carbon position of the cytosine base, facilitated by DNA methyltransferase (DNMT) enzymes. This modification can influence gene expression and subsequent protein expression without altering the primary DNA sequence, reflecting an organism's immediate adaptation to environmental exposures.

While DNA methylation is necessary for normal development and differentiation, it is susceptible to modulation by environmental factors such as diet, hormones, stress, drugs, or exposure to environmental chemicals. These chemicals include persistent organic pollutants like polychlorinated biphenyls (PCBs) and lead, which have been linked to neurodevelopmental issues and increased risk of autism spectrum disorders (ASDs). ASDs are characterised by impaired social communication and interaction, as well as increased repetitive behaviours and restricted interests.

The prevalence of ASD has been steadily increasing over the last 20 years, and while the cause of most cases remains unknown, there is a growing body of evidence suggesting a link between abnormal DNA methylation and ASD. Clinical studies have identified specific DNA methylation markers associated with ASD, and initial studies found promoter hypermethylation of MECP2 and UBE3A genes in post-mortem ASD brains. These genes are known to cause syndromic ASD when mutated. Further studies on animal models are needed to better understand the etiopathogenetic processes involved in ASD and to identify potential therapeutic targets.

Differences in DNA methylation patterns have also been observed in ASD patients compared to unaffected controls, particularly in younger individuals (aged ≤18), suggesting that 5hmC dysregulation may be specific to a developmental time point. Additionally, these differences were associated with genes important in psychiatric disease and development, such as those involved in cell-cell communication and neurological disorders.

While the technical advances and causative evidence are still being established, the understanding of DNA methylation in ASD may provide insights into gene-environment interactions and potential intervention strategies for neurodevelopmental disorders.

DNA methylation and metabolic syndrome

DNA methylation is a reversible biological signal and the most extensively studied epigenetic modulator in response to environmental stimuli. It is a dynamic process that is necessary for normal development and differentiation, but it is also susceptible to modulation by environmental factors such as diet, hormones, stress, drugs, or exposure to environmental chemicals.

Metabolic diseases such as diabetes and obesity are associated with profound alterations in gene expression that are caused by genetic and environmental factors. DNA methylation provides a mechanism by which environmental factors, including diet and exercise, can modify genetic predisposition to disease. Recent studies have found evidence that environmental factors at all ages could modify DNA methylation in somatic tissues, indicating that DNA methylation is a more dynamic process than previously thought.

Castellano-Castillo and colleagues analysed the impact of metabolic syndrome on the global DNA methylation pattern and the DNA methylation of several genes in visceral adipose tissue. They found positive correlations between the PPARA (gene encoding peroxisome proliferator-activated receptor-α (PPAR-α)) DNA methylation level and the metabolic syndrome index, triglyceride concentrations, and HOMA-IR (HOmeostatic Model Assessment for Insulin Resistance). This study provides an excellent example of the importance of epigenetics in metabolic syndrome.

Additionally, obesity has been associated with changes in gut microbiota, which can directly produce metabolites that play roles in epigenetic modifications, including DNA methylation and histone modification. These metabolites include folate, riboflavin, niacin, pantothenic acid, pyridoxine, and cobalamin. Identifying the correlation between changes in gut microbiota and DNA methylation is an important area of research.

While the studies mentioned above indicate a link between DNA methylation and metabolic syndrome, it is important to note that the current research on the epigenetic repercussions of exposure to a combination of pollutants is limited. Most studies focus on single-pollutant exposure, leaving room for further exploration of the effects of exposure to multiple-pollutant mixtures.

DNA methylation and industrial pollutants

DNA methylation is the most extensively studied epigenetic modulator in response to environmental stimuli. It involves the addition of a methyl group (-CH2) to the fifth carbon position of the cytosine base, a process facilitated by DNA methyltransferase (DNMT) enzymes. This modification can influence gene expression and subsequent protein expression without altering the primary DNA sequence.

Several studies have examined the link between DNA methylation and exposure to industrial pollutants, particularly air pollution. Air pollution is a complex mixture of particulate matter and gases produced by multiple industrial, commercial, and individual activities. Traffic-related air pollution (TRAP) is a significant source in urban environments, contributing to the development of cardiovascular disease, metabolic disorders, and lung pathologies such as asthma and chronic obstructive pulmonary disease (COPD).

Research suggests that exposure to air pollution often results in a widespread decrease in DNA methylation. For example, exposure to black carbon, a component of TRAP, has been associated with significantly higher DNA methylation in nasal brushings at cg23602092 in the promoter region of TET1. Similarly, exposure to NO2 during pregnancy has been linked to DNA methylation at three CpGs in cord blood samples, with potential roles in responses to reactive oxygen species (ROS).

In addition to air pollution, other industrial pollutants such as heavy metals and polycyclic aromatic hydrocarbons (PAHs) have been studied for their impact on DNA methylation. For instance, a study on individuals exposed to multiple industrial pollutants identified DNA methylation alterations that could be linked to metabolic changes and early health effects, including oxidative stress. Another study found that exposure to persistent organic pollutants was associated with global DNA hypomethylation in healthy Koreans and global DNA hypermethylation in an elderly population.

While the exact mechanisms remain unclear, these findings suggest that DNA methylation plays a crucial role in the interaction between gene functions and environmental stressors, potentially influencing health outcomes and the development of various diseases. Further research is needed to fully understand the complex relationship between industrial pollutants, DNA methylation, and their impact on human health.

DNA methylation and in utero exposure to pollutants

DNA methylation is the most extensively studied epigenetic modulator in response to environmental stimuli. It involves the addition of a methyl group (-CH2) to the fifth carbon position of the cytosine base, a process facilitated by DNA methyltransferase (DNMT) enzymes. This modification can influence gene expression and subsequent protein expression without altering the primary DNA sequence.

In utero exposure to pollutants has been linked to a range of adverse health outcomes, and DNA methylation is one mechanism through which these effects may occur. For example, in utero exposure to air pollution has been associated with an increased risk of neonatal problems, including prematurity and impaired fetal growth, as well as childhood cardiometabolic, respiratory, and neurodevelopmental disorders. Studies have found associations between in utero exposure to air pollutants and DNA methylation in placenta, cord blood, and childhood nasal tissue.

One study found a significant association between exposure to NO2 during pregnancy and DNA methylation at three CpGs in cord blood samples. The authors also identified two differentially methylated genes, thyroid peroxidase (TPO) and catalase, which may play roles in responses to reactive oxygen species (ROS). Another study found that exposure to O3 during the first trimester was associated with increased systolic blood pressure in 11-year-old children with particular DNMT1 or DNMT3B isoforms.

In utero exposure to other pollutants, such as diethylstilbestrol (DES), a synthetic estrogen, has also been linked to adverse health outcomes, including an increased risk of breast and vaginal cancer, preterm delivery, infertility, and early menarche. However, studies investigating the association between in utero DES exposure and DNA methylation in blood have had conflicting results, with some finding no evidence of persistent changes in DNA methylation.

Overall, while DNA methylation is a dynamic process that is necessary for normal development, it is also susceptible to modulation by environmental factors, including exposure to pollutants. Further research is needed to fully understand the complex relationships between in utero exposure to pollutants, DNA methylation, and health outcomes.

Frequently asked questions