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

It is crucial to note that histone alterations frequently Chromatin plays a pivotal role in a multitude of cellular
have an indirect effect by activating downstream signaling functions, encompassing DNA repair, DNA replication,
cascades through proteins. chromosome segregation, and signal transduction, among
others. Chromatin remodelers typically consist of multiprotein
3.4. Histone acetylation complexes and enzymes that harness adenosine triphosphate
Histone acetylation represents a reversible epigenetic hydrolysis to modify histones and reconfigure nucleosomes.
mechanism often associated with enhanced gene An example of chromatin remodeling is evident in the
transcription and implicated in processes underlying development of an embryonic heart. Mutations or defects
memory formation and drug addiction. It serves as a resulting from these remodelers can lead to a variety of
conduit for environmental cues, particularly those from cardiovascular disorders in adults. 85
drugs of abuse, to elicit targeted modifications in gene
expression. The enzymatic regulation of acetylation 3.6. Non-coding RNA (ncRNA) expression
involves histone deacetylases (HDACs) and histone ncRNA refers to RNA molecules transcribed from DNA
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acetyltransferases (HATs). During histone acetylation, a but not translated into proteins. There are four major
negatively charged acetyl group is affixed to lysine residues types of ncRNA involved in regulating gene expression:
on histone proteins, resulting in a relaxed chromatin MicroRNAs (miRNA), long ncRNAs (lncRNA), Piwi-
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structure conducive to transcription factor binding and interacting RNAs, and short interfering RNAs, all of which
heightened gene expression. have been extensively investigated. These regulatory
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Among histones, H3 and H4 are highly conserved and mechanisms play pivotal roles in managing transcription
have garnered significant attention due to their pivotal roles and translation, influencing chromatin remodeling, and are
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in chromatin organization. Histone acetylation often occurs integral to physiological processes as well as disease states.
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concomitantly with other chromatin modifications. Similar MiRNAs function by binding to target RNAs, thereby
to DNA methylation and demethylation, histone acetylation suppressing gene expression and inhibiting translation.
is anticipated to function as a biomarker for various diseases. They facilitate the transfer of genetic information within
A reduction in histone acetylation has been associated with cells, between different cells and tissues, and even across
neurodevelopment disorders, neural degeneration, plasticity, body fluids such as breast milk, sweat, urine, and blood.
and memory impairment. The CLOCK protein exemplifies Due to their involvement in cardiovascular disorders and
HAT and stands as a prominent transcription factor integral tumor suppression, miRNAs are considered excellent
to circadian rhythms and cellular homeostasis. Disruptions diagnostic markers. 60,64 In contrast, lncRNAs are more cell-
in this HAT cause a number of changes associated with sleep type specific and are expressed at lower levels compared to
deprivation and bipolar disorder manic-like behaviors. miRNAs. They primarily regulate transcription, which may
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A thorough investigation into histones will be essential for occur within or outside the nucleus. In addition, lncRNAs
the development of numerous therapeutic strategies for exhibit diverse functions, including regulation of mRNA
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psychiatric disorders, neurodegenerative diseases, and tumor within the cytoplasm of a cell.
cells. 4. The DRD2 gene as a therapeutic target

3.5. Chromatin remodeling for RDS
Changes to histone proteins can influence the structure of In a blinded study, Blum et al., demonstrated the initial
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chromatin, encompassing modifications such as acetylation, allelic association of the DRD2 gene with alcoholism. The
deacetylation, methylation, and demethylation. These study employed 70 brain samples collected from both non-
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modifications ultimately dictate whether transcription is alcoholics and individuals diagnosed with alcoholism. DNA
activated or repressed. Chromatin that is tightly condensed samples underwent digestion with restriction endonucleases
and transcriptionally inactive is termed heterochromatin, and were probed with a clone containing the complete 3’
where genes are typically silenced or inactivated. Conversely, coding exon, the polyadenylation signal, and approximately
euchromatin refers to loosely condensed chromatin that is 16.4 kilobases (kb) of non-coding 3’ sequence of the human
more accessible for transcription. In euchromatin, DNA is DRD2 gene (lambda hD2G1). The findings revealed that
readily accessible for binding by transcription factors and the presence of the A1 allele of the DRD2 gene accurately
other DNA-binding proteins, facilitating the regulation of classified 77% of the individuals with alcoholism, while
gene expression. The process of transitioning chromatin its absence correctly classified 72% of the nonalcoholics.
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from a condensed to a more accessible state is referred to This polymorphic pattern of the DRD2 gene suggested the
as chromatin remodeling, as discussed in earlier sections presence of a susceptibility gene for at least one form of
detailing histone modifications. alcoholism on the q22-q23 region of chromosome 11.

Volume 3 Issue 1 (2024) 5 https://doi.org/10.36922/gpd.1966