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Gene & Protein in Disease Stress-induced epigenetics of the DRD2 gene

is the most researched epigenetic biomarker due to its 3.2. DNA demethylation
chemical stability, role in mammalian development DNA demethylation is a process that occurs alongside
and disease, and its significant role in modulating gene DNA methylation but is not as widely understood. It
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expression across a wide array of biological processes. 54,55 serves as a biomarker for DNA damage, involving the
Although DNA methylation induces physical changes to removal of a methyl group from DNA, which can occur
gene structure, it is reversible in nature. Its primary function actively or passively in both dividing and non-dividing
is to impede DNA transcription, thereby suppressing the cells. Passive demethylation entails the loss of 5mC during
expression of specific genes. DNA methylation tests have DNA replication, while active demethylation involves
become more affordable and accessible and require only the alteration or removal of a methyl group from 5 mC.
a small amount of DNA, which can be obtained from Notably, 5 mC, a methylated form of cytosine, is commonly
body fluids, cells, or tissues. In addition, DNA can be utilized as a point of interest for gene mutations and as
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isolated from bacteria, viruses, plants, or mammals. DNA an epigenetic marker due to its regulatory role in gene
methylation is a biochemical process characterized by the transcription. 55,69
addition of a methyl group to DNA molecules. A common
occurrence is the addition of a methyl group to the 5-carbon Furthermore, a derivative of 5mC known as
position of a cytosine ring, forming 5-methylcytosine 5-hydroxymethylcytosine (5hmC) is abundantly present
(5-mC). DNA methylation assays are techniques in various organ tissues, particularly in the brain. DNA
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demethylation acts as a marker for DNA damage and
employed to quantify the levels of 5-mC within DNA facilitates repair processes by identifying potentially mutated
samples. The enzyme DNA methyltransferase (DNMT) sites. Primordial germ cells of an embryo and developing
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plays a pivotal role in catalyzing DNA methylation, zygotes are the primary sites where demethylation occurs,
particularly at CpG dinucleotide sites. Notably, DNMT-1 emphasizing its key role in differentiation mechanisms. 71
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is primarily responsible for DNA replication in the mitotic
cells of the brain, which exhibit the highest levels of DNA DNA demethylation is mediated by enzymes from
methylation in the body. DNMT-3A and DNMT-3B, on the ten-eleven translocation (TET) family. 72,73 The TET
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the other hand, regulate methylation patterns during early enzymes function as tumor suppressors in various
developmental stages. 59 malignancies, and their loss or dysfunction is closely
associated with rapidly mutating cancers. In addition,
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NA methylation plays a critical role in early brain thymine DNA glycosylase plays a crucial role in DNA
development and the specification of regions through gene demethylation and normal development by initiating base
expression. It also significantly influences mutational excision repair, which is essential for repairing damaged
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events associated with various cancers, increasing the DNA throughout the cell cycle. 75
risk of gene mutations and the inactivation of specific
tumor-suppressor genes. 60-64 For instance, exposure to In summary, DNA demethylation serves as a mechanism
environmental carcinogens, such as pollution, can induce for epigenetic reprogramming of genes, influenced by
mutations in genes responsible for DNA methylation, environmental risk factors such as injuries and substance use.
leading to altered cellular states such as proliferation or 3.3. Histone modification
differentiation and ultimately resulting in cancer. 64
Histones, a class of proteins, facilitate the packaging of
Moreover, DNA methylation is involved in genomic DNA into structural units known as nucleosomes. This
imprinting, a process where genes are silenced or inactivated packaging provides structural support and ensures that
through DNA methylation. Imprinting occurs when one DNA fits appropriately within the nucleus of the cell. The
allele from either the father or mother is silenced, resulting modification of histones exemplifies epigenetic regulation,
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in an imprinted gene. These parent-of-origin effects can be as it influences transcription and alters phenotypes in
inherited by gametes and passed down to offspring, giving response to environmental stimuli and stressors. Histone
rise to various diseases such as Prader-Willi syndrome and modifications achieve this process by tightly compacting
Angelman syndrome. 66,67 This mode of inheritance also aids DNA, hindering its accessibility to the cellular machinery.
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in understanding the role of DNA methylation in psychiatric Conversely, histone relaxation facilitates increased access
disorders such as major depressive disorder, bipolar of proteins to DNA, thereby enhancing its susceptibility
disorder, schizophrenia, autism, and related conditions. to analysis by the cell. Histone alterations have also been
This finding is significant as it provides crucial insights into found to affect DNA repair and replication, in addition
how abnormalities in this mechanism contribute to the to cell state modifications. They are also utilized to
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pathophysiology of diverse disorders, and it suggests the synthesize macromolecules like lipids and carbohydrates,
potential of DNA methylation as a therapeutic target. 67 as well as to regulate cell metabolism and energy outputs.
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Volume 3 Issue 1 (2024) 4 https://doi.org/10.36922/gpd.1966