Deeper Than Genes: The Role of Epigenetics in Shaping Human Development
PSYC 4034-Psychological Psychology
Dr. Vincent EscandellDecember 3, 2018
The concept of epigenetics has become an essential part of human development. The epigenetic mechanisms of positive feedback loops, DNA methylation, and histone modifications affect the RNA sequence by altering the gene expression before translation occurs. Cell memory helps newly developed to recognize what kind of cells they are. Cell memory can be carried out through positive feedback loops. Positive feedback loops happen during the action potential which is responsible for the firing of neurons in the brain, which sends signal to other parts of the body to carry out tasks. DNA methylation adds or takes away a methyl group of a cytosine base. Hypermethylation or hypomethylation can lead to the development of mental illness such as anxiety, bipolar disorder, and suicidal thoughts. Histone modifications involve the wrapping of DNA around histones. The cycle of restoration and recognitions allows one histone to be passed down from one generation to the next while the newly synthesized histones allow for genetic variation. Experiences or environment cues, along with these mechanisms alter brain plasticity, which allows synapses in the brain to be modified. The sum of epigenetic mechanisms and environmental cues had led many to believe that human development is “deeper than genes.”
According to Garrett & Hough (2018), epigenetics is a change in the gene expression without modifying the DNA sequence (p. 164). The word itself means “on or upon genetics” (A. Auger, 2017; C. Auger, 2017). The purpose of epigenetics is to alter the RNA sequence before it is translated into proteins. The mechanisms that alter gene expression are positive feedback loops, DNA methylation, and histone modifications. Molecular guidance cues also known as genetics are paired with patterned neural activity, or experience, are paired together to affect brain plasticity. The mechanisms that alter gene expression are positive feedback loops, DNA methylation, and histone modifications. Molecular guidance cues also known as genetics are paired with patterned neural activity, or experience, are to affect brain plasticity. Epigenetics alters the plasticity of the brain through positive feedback loops, DNA methylation, and histone modifications which are responsible for shaping human cognition, personality, mental health, and behavior.
Positive feedback loops shape human cognition by allowing daughter cells to
“remember” what kind of cells they are which are responsible for development. According to Alberts et al. (2014), proliferating cells “maintain its identity” by the process of cell memory, which are patterns of gene expression that contain nongenetic information that can be passed down from parental cells to daughter cells (p. 279). The concept of cell memory explains the process of migration in the development of neurons. After proliferation, the newly developed cells migrate to their eventual locations. For instance, this could explain why brain cells do not migrate to the heart. It is cell memory which is responsible for this.
Cell memory can be created by positive feedback loops. Positive feedback loops are when the output of a reaction or chemical pathway stimulates the original activity. When cells divide, a transcription regulator is distributed to both daughter cells and continues to stimulate the positive feedback loop. By repeating this stimulation, the transcription regulator will continue to be produced in the following cell generations. Positive feedback loops establish a cycle of gene expression that pushes the system out of homeostasis so that the gene expression can be transmitted.
The action potential traveling down the axon is an example of the positive feedback loop. Hodgkin & Huxley (2001), conducted an experiment in which they created a model to test whether the electrical conductivity of sodium and potassium alone could power the action potential. When the sodium voltage gate is activated, there is an increase in the entry of sodium into the neuron, causing the membrane potential to depolarize. The depolarization leads to a greater conduction of electrical signals, the entry of more sodium atoms, and further depolarization. The positive feedback continues until electrical conductivity activates the potassium gate. Once the positive feedback loop begins, it is continued by the essential properties of the neuron as well as the voltage dependence of the gates, the action potential is defined as being “regenerative.” Due to this characteristic, the action potential has an uncompromising behavior. The action potential is important to epigenetics because the firing of the neurons sends messages and signals to the brain which sends signals to the rest of the body.
Another example of positive feedback is childbirth. A stimulus produces a change in homeostasis, causing the cervix to dilate. This change is detected by cervix receptors and the information is sent to the hypothalamus. The information is sent to the smooth muscle receptors. The response is intensified, and the body goes back to homeostasis.
DNA methylation is epigenetic mechanism that shapes human behavior by and alters the plasticity of the brain by modifying the cytosine DNA bases. The process of DNA methylation involves attaching a methyl group to the CpG sites, which are the cytosin-phosphate-guanine nucleotide sequences (A. Auger, 2017; C. Auger, 2017, pg 450). The structure cytosine becomes 5-methylcytosine. The methyl place is responsible for the marked place on DNA. The enzyme called DNA methyltransferases helps to transfer the methyl group to the fifth atom. This enzyme are expressed in the central nervous system and are controlled during development. The location of the methylated cytosine and the period of development in which methylation occurs has an impact on the effect of DNA methylation on gene function.
DNA methylation at the CpG sites leads to gene expression and also aids in activating gene transcription. According to Dupont, Armant, and Breener (2009), there is evidence that suggest that non-CpG sequences are methylated as well as CpG sequences (p. 1). DNA has regulatory gene regions called silencers and promoters, which are responsible for turning a gene off or on. The promoter regions of silenced genes contain more methylated cytosine compared to actively transcribed genes, which impacts transcriptional repression. The methylation of cytosine may repress gene expression by preventing the specific transcription factors from binding. In other words, DNA methylation turns a gene “off” which results in an inability of the genetic information to be read from DNA. Removing the methyl group activates the gene and turns it “on.” The mechanism is useful because it ensures that genes are only expressed when they are needed. DNA methylation patterns can be inherited after DNA replication, daughter cells will contain one methylated DNA strand which is inherited from one parent, and another newly synthesized unmethylated strand. An enzyme called maintenance methyltransferase interacts with the helices to ensure that CG sequences are base paired together (Alberts et al., p. 280)
An example of DNA methylation that affects plasticity is the inherited personality traits. In 2008, there was a study conducted on the epigenetic differences between reactions to stress among monozygotic twins. The monozygotic twins in the study had different life paths. One twin demonstrated risk-taking behaviors and while the other one did not. It was discovered that the twins had differences in DNA methylation of CpG islands, which are short strands of DNA with a high frequency, near the homeobox DLX1 gene, which is responsible for the formation of body structures during embryonic development, could modify stress responses and risk-taking behaviors.
DNA methylation can also affect mental health because hypermethylation and hypomethylation can release chemical into the brain, predisposing a person to changes in personality and mental health issues. Hypothalamic-pituitary-adrenal, known as HPA, alters the HPA stress responses in humans who experienced child abuse. Increased levels of HPA increase the risk of suicide. A study conducted by Owens (2009), studied the brain tissue of 24 people who were suicide victims with a history of child abuse were examined. It was discovered that these people had decreased levels of glucocorticoid receptor gene promoter was more methylated in child abuse victims.
There is also evidence of hypomethylation of a gene promotor of a prefrontal lobe enzyme in dead brains samples from people who had bipolar disorder. A study conducted by Abdolmaleky et al. (2006) researched the dead brain tissues of people who had bipolar disorder. It was concluded from this study that catechol-O-methyl transferase, an enzyme responsible for metabolizing dopamine at the synapse, was hypomethylated. Evidence suggest that the hypomethylation of the promoter results in over-expression of that enzyme, leading to
The last epigenetic mechanism that affects brain plasticity are histone modifications. Histone modifications are important for neuronal functioning and brain development (A. Auger, 2017; C. Auger, 2017, p. 453). The addition of an acetyl group to histones through histone acetyltransferases is the most well-known. DNA has a negative charge and histones have a positive charge. The opposite charges result in DNA that is coiled tightly. The additions of acetyl groups neutralize the charge on the histone spools, causing the DNA to slightly unwind and making the DNA thread more easily accessible for transcription factors, which regulate gene transcription. Male mice have higher levels of acetylation of a specific histone protein compared to females in late prenatal life and disappears in postnatal life. It is believed that histone modifications are responsible for creating sex differences due to the disruption histone deacetylases, which remove methyl groups. When the histone is removed, the histone has its positive charge and gene transcription is reduced.
When chromosomes are replicated, the resident histones are distributed randomly to each of the two daughter DNA double helices (Alberts et al., 2014, p. 281). Nucleosomes are the building blocks of chromatin. Nucleosomes consists of octamer histones. Each octamer has two units of each principle or variant histone H2A, H2B, H3, and H4. A linker protein pulls the nucleosomes together and pack them into a more compact chromatin fiber. As a result, each daughter chromosome will inherit half of its parent’s modified histones. Enzymes are responsible for catalyzing the spread of modifications to new histones. The cycle of modification and recognition can restore the parental histone modification pattern allow the inheritance of the parental chromatin structure.
Changes in histone modification alter cognition by influencing long term memory formation (Weaver, 2018). This is done by altering chromatin accessibility and the way genes are expressed, which are responsible for memory and learning. Increases in histone acetylation and alterations in histone methylation promote the formation of transmission signals to the synapse, promoting gene expression. Neuronal increases in histone deacetylase activity, causes gene silencing, resulting in reduced synaptic plasticity and impairs memory.
In a study conducted by Graff et al. (2012), the post-mortem brain of people with Alzheimer’s disease showed that cognitive capacities in their brains are compelled by blocking gene transcription. The blockage was mediated by histone deactylase II. Histone deacetylase II reduces histone acetylation of genes that are important for memory and learning, which decrease gene expression. From the study, it was concluded that Alzheimer’s patients had an increase in histone deacetylase levels.
Positive feedback, DNA methylation, and histone modifications are all epigenetic mechanisms that alter the plasticity of the brain. Plasticity is the ability of the synapses in the brain to be modified (Garrett ; Hough, 2018). In the steps of neural development, the process of differentiation involves the development of axons and dendrites to develop its unique shape. The process of myelination is when the glia produces a fatty sheath that speeds the transmission of neural impulses. It is not until the last stage, synaptogenesis, that the synapses are able to modified. The speed at which neurons are fired vary depending on age.
There are two principle of plasticity. The first principle of plasticity states that from the time a person is born until the time of adolescence, the brain is “conducive to axonal growth, and cellular mechanisms are optimal for promoting the formation strengthening, weakening, and elimination of synapses” (Garrett ; Hough, 2018, p. 69). The first principle of plasticity means that from the time a person is born to about age 12, known as the critical period, the brain is going through constant changes, which make it easier to learn new things. For example, it would be easier for a person who is 12 years old or younger to learn a new language of musical instrument because their brain is making new connections and associations. The reason for this is due to the fact that the brain is still in the process of myelination which means the nervous system has not fully developed. This ties in with the epigenetic mechanisms because the younger a person is, the easier it is to modify the RNA sequences before they are translated to proteins, which carry out functions. Therefore, it is easier to retain plasticity, modifying the gene expression by experience.
The second principle of plasticity is no particular pattern of connectivity that is firmly entrenched in a developing circuit so there is less to overcome. This principle means that after the age of 12, that the brain is going through myelination, which causes changes in behavior. Because the brain does not have new patterns of connectivity, it makes it more difficult for the brain to make connections and associations for learning. For example, it would be harder for a person past the age of 12 to learn a new language or a new instrument because the neural activity that is stimulated by experience is sharpened and realign patterns of connectivity. Once the pattern of connectivity is established, it is harder for the modify RNA sequences through experience and alter the gene expression before it made into proteins.
In conclusion, epigenetics alter the plasticity through three mechanisms: positive feedback loops, DNA methylation, histone modifications. These mechanisms are responsible for shaping human cognition, behavior, personality, and mental health. Positive feedback loops force the system to be pushed out of homeostasis, leading to gene transmission of gene expression. DNA methylation alters the cytosine bases on DNA to turn genes on or off during certain times of the days or certain times in our life. Histone modifications are altered by enzymes that affect gene expression responsible for neural function and brain development. The sum of epigenetic mechanisms and environmental cues alter our brain plasticity which explain differences in behavior and helped to explain why certain people are predisposed to certain diseases.
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