# Environmental epigenetics

Environmental epigenetics is a branch of epigenetics that studies the influence of external environmental factors on the gene expression of a developing embryo. The way that genes are expressed may be passed down from parent to offspring through epigenetic modifications, although environmental influences do not alter the genome itself.
During embryonic development, epigenetic modifications determine which genes are expressed, which in turn determines the embryo's phenotype. When the offspring is still developing, genes can be turned on and off depending on exposure to certain environmental factors. While certain genes being turned on or off can increase the risk of developmental diseases or abnormal phenotypes, there is also the possibility that the phenotype will be non-functional. Environmental influence on epigenetics is highly variable, but certain environmental factors can greatly increase the risk of detrimental diseases being expressed at both early and adult life stages.

## Environmental triggers for epigenetic change

The way that genes are expressed is influenced by the environment that the genome is in. These environmental influences are referred to as triggers and can involve anything that influences normal gene expression. How the genome is expressed depends on the environmental factors present during gestation. It is possible for the environmental effects of epigenetics to be deleterious or to be a natural part of the development pathway. When these environmental factors are detrimental it causes the deactivation of some DNA sequences, which can lead to atypical phenotypes. Some of the most common triggers include diet, temperature, exposure to harmful substances, and lifestyle. These triggers can cause low birth weight, neurological disorders, cancers, autoimmune diseases, and many other malformations.
These epigenetic triggers can change the way that an organism develops and have lifelong effects. Epigenetic changes can be passed down through offspring, present in multiple generations, and continue to change throughout a lifetime. Each sequence of affected DNA is not expressed at the same time. There are specific stages in which these expressions happen during development. The combined epigenetic mechanisms of DNA methylation and histone modification are responsible for how the genome is altered. For example, the suppression of oncogenes is regulated by DNA methylation and whether or not methylation is activated. This activation depends on the environment. When these activations happen, they can be passed down to the next generation through germ-cell differentiation.

### Examples of triggers
#### Nutrients

Offspring can experience phenotypic changes depending on their access to nutrients. When nutrients are limited during pregnancy, the offspring's phenotypic expression can be disrupted. Nutrient intake is also important during lactation for the purpose of transferring nutrients to the offspring.

#### Stress during pregnancy

When the maternal figure is exposed to stressors it can lead to a greater likelihood of expressing or stunting DNA expression. If the maternal figure experiences high levels of depression or stress it can lead to small litter sizes with lower birth rates. Decreased hormone production is the suspected cause of this.

#### Temperature

Changes in temperature can have varied effects on an organism. DNA methylation can be impacted by temperature when the temperature deviates from its normal value, preventing regular processes from taking place. Temperature can be considered a stressor in environmental epigenetics since it has the potential to change how offspring respond and react to their environment. Monarch butterflies are an example of how temperature can impact the survival and fitness of an organism. If exposed to stressors such as varying temperatures, these butterflies may express coloring that deviates from their normal color.

#### Lifestyle choices

Epigenetic marks can result from a number of exposures and choices made by an individual in their lifetime. Exposure to environmental pollutants, psychological stress, dietary choices or restrictions, working habits, and consumption of drugs or alcohol all influence the epigenetics of an individual and what may be passed down to future offspring. Such exposures can affect important processes of epigenetics such as DNA methylation and histone acetylation, influencing the risk for noncommunicable diseases such as obesity.

## Exposure

Exposure to certain materials or chemicals can cause an epigenetic reaction. The epigenetic causing substances cause issues like altered DNA methylation, CpG islands, chromatin, along with other transcription factors. Environmental epigenetics aims to relate such environmental triggers or substances to phenotypic variation. Numerous studies have demonstrated how exposure to environmental pollutants, such as heavy metals, pesticides, and air pollutants, can induce epigenetic changes in various organisms. For example, research has shown that exposure to pollutants like biphenol A (BPA) and polycyclic acromatic hydrocarbons (PAHs) can lead to DNA methylation changes and histone modifications in plants, animals, and humans.
Epigentic mechanisms play a role in the adaptation of species of changing environmental conditions, including climate change. Studies have shown that organisms can exhibit phenotypic plasticity through epigenetic modifications in response to environmental stressors such as temperature fluctuation, drought, and habitat loss.
Environmental epigenetics has revealed the potential for transgenerational effects, where environmental exposures experienced by one generation can influence the phenotypes and health outcomes of subsequent generations through epigenetic inheritance mechanisms. Studies in various organisms, including plants, insects, and mammals, have shown transgenerational epigenetic effects resulting from parental exposure to stressors such as toxins, dietary changes, and environmental contaminants. Epigenetic modifications can influence gene expression and phenotypic traits in oragamisms across different trophic levels, with implications for ecosystem stability.

### Lemon sharks

An example of exposure causing environmental epigenetic can be seen in lemon sharks, Negaprion brevirostris. Due to a dredging event, lemon sharks in the Bahamas experienced an epigenetic change. Dredging is done with a machine that clears out all mud and debris found at the bottom of a body of water. Dredging is extremely harmful to the physical environment and the organisms living there. This dredging caused exposure to different toxic metals like Manganese along with other trace amount of heavy metals, which then affected DNA methylation in juvenile lemon sharks. This exposure caused the lemon sharks’ DNA to methylate at abnormal rates which caused gene expression to be altered. Scientists hypothesized that this aberrant DNA methylation could be caused by the stress that the dredging caused. Exposure to a stressful event is also an example of an environmental epigenetic factor.

### Plants

Plants need some types of metals to help with their development, but when exposed to high amounts, the metals can become toxic to plants. Since plants can process metals that are important for their growth, they also process metals that are not needed to help them grow and develop. Once the levels of the metals get too high, they start to affect plants directly and indirectly because metals cannot be broken down. Direct toxic effects that occur due to high levels of metal are inhibition of cytoplasmic and damage to the structure of the cell because of oxidative stress. Oxidative stress is like a bad storm that messes up the plant by damaging it so it cannot get the nutrients it needs to be healthy because things that are not supposed to be there are taking up space where the essential nutrients should go. Indirect toxic effects are the proxy nutrients at the plant's cation exchange. The cation exchange site is where the plant picks up the nutrients it needs, though if something comes in and starts taking all the valuable nutrients, such as heavy metal, there is nothing there to help the plant grow. An example of a heavy metal that is not required for plant growth is mercury. The relationship between Hg in the soil and how much plants take in is complex. It relies on many other factors, such as the pH of the soil, the type of plant species, etc.
Many types of heavy metals are toxic to plants, such as lead. Typically, land plants absorb lead(Pb) from the soil, most retaining it in their roots with some evidence of foliage uptakes and potential distribution to other plant parts. Calcium and phosphorus can reduce the uptake of lead, a common and toxic soil element that impacts the plant, growth structure, and photosynthesis of the plant. Lead, in particular, inhibits the process by which a plant grows from a seed into a seedling, known as seed germination in various species, by interfering with crucial enzymes. Studies have shown that lead acetate reduces protease and amylase activity in rice endosperm considerably. This interferes with early seeding growth across plant species such as soybean, rice, tomato, barley, maize, and some legumes.
Furthermore, lead delays root and steam elongation and leaf expansion, with the extent of root elongation inhibition varying based on the lead concentration, the medium's ionic composition, and pH. Soil levels that have high levels of lead can also cause irregular root thickening, cell wall modifications in peas, growth reduction in sugar beets, oxidative stress due to increased reactive oxygen species (ROS) production, biomass, and protein content in maize, along with diminished lead count and area, plant height in Portia trees, and enzyme activity affecting CO2 fixation in oats.
Manganese (Mn), is crucial for plants and involves in photosynthesis and other physiological processes. Deficiency commonly affects sandy, organic, or tropical soils with a high pH above six and heavily weathered tropical soils. Mn can move easily from roots to shoots, though it is not efficiently redistributed from leaves to other parts of the plant. The signs of Mn toxicity are necrotic brown spots on leaves, petioles, and steams that start on the lower leaves and move upward, leading to death. When damage to young leaves and stems, coupled with chlorosis and browning, called a "crinkle leaf." In some species, toxicity can begin with chlorosis in older leaves, advancing to younger ones, and can inhibit chlorophyll synthesis by interfering with iron-related processes. Mn toxicity is more present in soils with a pH level lower than six. In the broad bean plant, Mn affects shoot and root length The spearmint plant, lowers chlorophyll and carotenoid levels and increases root Mn accumulation. Pea plant, lowers chlorophyll a and b, growth rate, and photosynthesis. In the tomato plant, it slows growth and decreases chlorophyll concentration.

### Humans

Humans have displayed evidence of epigenetic changes such as DNA methylation, differentiation in expression, and histone modification due to environmental exposures. Carcinogen development in humans has been studied in correlation to environmental inducements such as chemical and physical exposures and their transformative abilities on epigenetics. Chemical and physical environmental factors are contributors to epigenetic statuses amongst humans.
Firstly, a study was performed on drinking water populations in China involving three generations: the F1 generation consisting of grandparents exposed to arsenic in adulthood, the F2 generation including the parents exposed to arsenic in utero and early childhood, and the F3 generation which were the grandchildren exposed to arsenic from germ cells. This area in China was historically known for its dangerously high levels of arsenic, therefore, there was opportunity to examine the timeline As exposures across the three generations. The study was conducted to discover the linkage between the timeline effects of As exposure and DNA methylations. The population and environment for which the study was conducted were reportedly not exposed to other environmental exposures besides arsenic.
The results concluded from this experiment were that 744 CpG sites had been differentially methylated. The 744 sites were found across all three generations in the group exposed to arsenic. The concluding argument based on the results of this study is that the DNA methylation changes were more prevalent in those that developed arsenic-induced diseases.
Exposures to environmental factors during human lifetimes and their potential effect on phenotypes is a highly question topic involving epigenetics and disease development. In the case of humans, "unhealthy" phenotypes have been identified to carry such evidence that environmental epigenetics could be a leading cause in gene regulation, disease development, cell development and differentiation, aging, and carcinogenic effect. Although the way that environmental factors and the human genome work together is not completely understood, their influence has been identified and is continuing to drive explanations for human genome modifications and their outcomes. Driving evidence for adverse effects implemented by extrinsic factors from the environment, comes from studies done on nutrition and exposures to toxins.
Besides arsenic exposures, other metals have been identified to cause such hypermethylations. Concentrations of Cd, Cr, Cu, Pb and Zn metals were identified in fishermen's blood and resulted in an increase in the expression of the IGF2 gene. The IGF2 gene is responsible for making the insulin-like growth factor 2. The insulin-like growth factor is involved in growth and can result in disorders where cell growth and overgrowth are abnormal. Such disorders include breast and lung cancers and Silver–Russell and Beckwith–Wiedemann syndromes The significance of IGF2 gene expression is found in its relationships to human health. There is remaining uncertainty between the long-term environmental exposures and epigenetic changes, but conducted research has provided that heavy metal exposures cause DNA methylation changes.
Exposures to certain triggers such as alcohol or drugs can disrupt the normal expression of the offspring's phenotype. Antipsychotic drugs can lead to abnormal or stunted development during the fetal or embryonic stages.

## Multigenerational epigenetic inheritance

Organisms respond to the habitat around them in many different ways, one way is by changing its gene expression to one that is most suitable for their surroundings. More often than not, this has a direct correlation to phenotypic plasticity. Phenotypic plasticity is when a species develops new physical features in response to the environment they’re in. Passing down epigenetics that are in relation to mitotic cell divisions allows for the belief of a possibility that this is also passed down from parents to offspring. Parents could be responsible for the development of new phenotypes in these cases.

### Epigenetic inheritance

Epigenetic inheritance refers to passing down or transferring epigenetic information between the parent and offspring. Some believe that these occurrences can be passed down for many generations. For example, the language a given species utilizes develops a specific phenotype that will be passed down from generation to generation.

### Cultural inheritance

Cultural inheritance is a behavioral factor that is passed down from generation to generation, similar to inheritance. For example, in rats, mothers that lick and groom their pups pass down a specific behavior to their offspring causing them to do the same to the subsequent generation. Epigenetic inheritance is involved in this, but they are separate things that work together.

## Mechanisms influencing epigenetics
### DNA replication

DNA replication is a highly conserved process involving the copying of genetic information from parent one generation to the next. Within this complex process, chromatin disassembles and reassembles in a precise and regulated manner in order to compact large amounts of genetic material into the nucleus, while also maintaining the integrity of epigenetic information carried by histone proteins bound to DNA in the process of cell division. Half of the histones present during replication are from chromatin found in the parent DNA and thus carry the parent's epigenetic information. These epigenetic marks play a critical role in determining chromatin structure and thus gene expression in the newly synthesized DNA. The other half of the histones present in replication are newly synthesized.

### DNA methylation

A major formative mechanism of epigenetic modification is DNA methylation. DNA methylation is the process of adding a methyl group to a cytosine base in the DNA strand, via covalent bond. This process is carried out by specific enzymes. These methyl additions can be reversed in a process known as demethylation. The presence or absence of methyl groups can attract proteins involved in gene repression, or inhibit the binding of certain transcription factors, thus preventing methylated genes from being transcribed, ultimately affecting phenotypic expression.

### Acetylation

Acetylation is a reaction that introduces an acetyl group into an organic chemical compound, typically by substituting an acetyl group for a hydrogen atom. Deacetylation is the removal of an acetyl group from an organic chemical compound. Histone acetylation and deacetylation affect the three-dimensional structure of chromatin. A more relaxed chromatin structure leads to greater rates of genetic transcription, whereas a tighter structure inhibits transcription.

### Transcriptional regulation

Transcriptional regulation is a complex process involving the binding of transcriptional machinery to regulatory proteins—specifically chromatin remodeling or modifying proteins-directly onto a specific target. This may sometimes be facilitated by the contribution of accessory complexes that function primarily to repress and activate transcription in a cell. Transcriptional regulation additionally focuses on the epigenetic regulation of a target locus, as the epigenetic status of the locus determines either the facilitation of or prohibition of transcription. Epigenetic regulation is necessary for the precise deployment of transcriptional programs.