EPIGENETIC

1. What is epigenetic mean?

- How the DNA interacts with the multitude of smaller molecules found within cells
which can activate and deactivate genes
- Epigenetics is the study of how your behaviors and environment can cause
changes that affect the way your genes work. Unlike genetic changes, epigenetic
changes are reversible and do not change your DNA sequence, but they can
change how your body reads a DNA sequence. epigenetic changes affect gene
expression to turn genes “on” and “off”.
- Epigenetic factors: epi (above, above genome) -> factors that change how the
genome expressed.

2. Example of epigenetic state in a cell stage!

- the process of cellular differentiation. During morphogenesis, totipotent stem
cells become the various pluripotent cell lines of the embryo, which in turn
become fully differentiated cells. In other words, as a single fertilized egg cell –
the zygote – continues to divide, the resulting daughter cells change into all the
different cell types in an organism, including neurons, muscle
cells, epithelium, endothelium of blood vessels, etc., by activating some genes
while inhibiting the expression of others. SAME GENOME TP OWN DISTINCT
EPIGENOME
- allows for cell specialization during gamete development, while retaining the
potential for returning to the ground state of totipotency after fertilization.
- Epigenetuic marks on genes can be cleared for development (when producing
gametes and also after fertilization)
- CONTOHNYA kan awalnya same genes but look and act differently. Nerve cell vs
muscle cell -> same DNA but work differently. Epigenetics allows the muscle cell
to turn on genes to make proteins important for its job and turn off genes
important for a nerve cell’s job

3. Example of epigenetic state in an organism!

- Agouti trait in mice -> activated agouti gene can affect the color, obese, prone to
other diseases.
 - Tubercolosis -> mycobacterium tuberculosis. Infections with these germs can
cause changes to histones in some of your immune cells that result in turning off
the IL-12B gene. Turning off itu weakens ur immune system and improves the
survival of Mycobacterium tuberculosis.
- Cancer ->

4. Epigenesis mechanism
Terdapat tiga sistem yang dianggap dapat memulai dan mempertahankan
perubahan epigenetic, yaitu metilasi DNA, modifikasi histon, dan non coding RNA.
HOWWW? Genes in DNA are expressed when they’re read and transcribed into
RNA, yg selanjutnya translated into proteins. Proteins -> determines a cell’s
characteristics and function. EPIGENETIC CHANGES CAN BOOST OR
INTERFERE THE TRANSCRIPTION OF SPECIFIC GENES. Bisa di dna nya,
protein histonnya, (chemical tagnya namanya epigenome -> contohnya ada methyl
group yang inhibit gene expression -> prevent transcription factors from binding.
Atau causing the DNA to coil more tightly (unaccessible)
a. DNA Methylation: DNA methylation works by adding a chemical group to DNA.
Typically, this group is added to specific places on the DNA, where it blocks the
proteins that attach to DNA to “read” the gene. This chemical group can be
removed through a process called demethylation. Typically, methylation turns
genes “off” and demethylation turns genes “on.”
Methylation can prevent transcription factors from binding.
Example: perbedaan bentuk bunga dan warna buah are due to inherited differences
in the level of promoter methylation. Methylation of DNA in plants controls such
developmental characteris
b. Histone modification: DNA wraps around proteins called histones. When
histones are tightly packed together, proteins that ‘read’ the gene cannot access
the DNA as easily, so the gene is turned “off.” When histones are loosely
packed, more DNA is exposed or not wrapped around a histone and can be
accessed by proteins that ‘read’ the gene, so the gene is turned “on.” Chemical
groups can be added or removed from histones to make the histones more
tightly or loosely packed, turning genes “off” or “on.” Modified histons ->
gaharus epigenetic factors ada di dna nya langsung, tp di histonnya bisa ikut
meregulasi gen
 c. Non Coding RNA: Your DNA is used as instructions for making coding and non-
coding RNA. Coding RNA is used to make proteins. Non-coding RNA helps
control gene expression by attaching to coding RNA, along with certain proteins,
to break down the coding RNA so that it cannot be used to make proteins. Non-
coding RNA may also recruit proteins to modify histones to turn genes “on” or
“off.”

5. Example for each epigenesis mechanism

a. DNA Methylation:
- Cancer: hypomethylation of DNA in cancer cell genomes, which caused
overexpression of genes within that cell. Other studies have shown
hypomethylation of pro-proliferative genes like BAX2 that are suppressed in
normal cells. [28] Other reports show hypermethylation of tumor suppressor
genes, like Rb, BCRA1, and CDKN2A, in cancer cells. Such as colon, breast,
liver, bladder, Wilms, ovarian, esophageal, prostate, and bone cancers. there are
many differential DNA methylation related to cancers, such as hepatocellular
carcinoma, glioblastoma, breast cancer, squamous cell lung cancer, thyroid
carcinoma, and leukemia.
- Autoimmune diseases: Autoimmune diseases are caused by low activity or over
activity of the immune system. Immune cells are the primary targets in disease
and are easily accessible from the blood, making them a relatively good model for
studying the link between DNA methylation and phenotypes.
1. RA -> chronic autoimmune inflammatory disease. Altered DNA methylation
of human leukocyte antigen (HLA) can increase the risk of developing RA.
2. SLE -> autoimmune disease which the immune system mistakenly attacks
healthy tissue. Teridentified differential DNA methylation in SLE patients in
genes involved in autoantibody production. In peripheral blood of SLE
patients, low levels of DNA methylation was observed in the promoter of IL-6
gene.
3. MS -> main cause of neurological disability in young aduls, chronic
inflammatory and neurodegenerative disease that is self-immune mediated.
Changes in DNA methylation have been observed in multiple immune cell
types in MS patients including CD4+ T cells, CD8+ T cells, and CD44+
 encephalitogenic T cells,53 and it is also altered in the hippocampi of patients
with MS after demyelination. Smoking juga risk factor for MS, can alter the
DNA methylation level in MS patients through the interaction of major genetic
risk factors.
- Metabolic disorders: hyperglycemia (type I [insulin gadiproduksi, islet cells
diattacked] and II [less insulin, becomes resistant to insulin] diabetes),
hyperlipidemia (obesity-related condition).
1. T2BM: Type 2 diabetes mellitus (T2BM) is a complex disorder caused by a
series of factors including genetics, epigenetics, and environmental factors. A
comparison of the methylation level of islets in patients with T2BM with those
from normal donors showed that a series of sites had different DNA
methylation levels which led to differential gene expression
2. Obesity is another common disease in which the environment plays an
important role. Genome-wide analysis showed that increased DNA
methylation of hypoxia-inducible factor 3 alpha in both blood cells and
adipose tissue is associated with an increased body mass index (BMI).
- Neurological disorders
- Aging
- Genomic imprinting: Genetic imprinting is an epigenetic phenomenon in which
the maternal and paternal alleles are expressed in a parent-of-origin-specific
manner.
b. Histone modification: acetylation (higher gene expression), methylation
(transcriptionally permissive), phosphorylation (activating/permissive), and
ubiquitination (repressive, activating/permissive).
1. Allergic inflammation: histone modifications, which contribute to the lineage
commitment, differentiation and maturation of immune cells, including those
strongly involved in allergic inflammation such as CD4+ T-helper (Th) cells,
are likely to play a crucial role in the predisposition to developing atopic
diseases as well as in the effector phase of allergic inflammation
2. Respiratory tract allergic inflammatory disease
3. Inflammatory disorders of the lung
4. Nasal chronic rhinosinusitis and polyposis
6. X inactivation
 X inactivation represents a complex multi-layer epigenetic mechanism that
profoundly modifies chromatin composition and structure of one X chromosome in
females. Untuk menyeimbangi -> X upregulation of expressed genes in males and
females, and X inactivation or silencing of one X chromosome in females. a
mechanism that results in silencing of a randomly chosen X chromosome in early
female embryogenesis. WHY? Because females receive two X chromosomes, they
inherit two copies of many of the genes that are needed for normal function. An
example is Down’s syndrome, which is caused by an extra copy of part or all of
chromosome 21. In female mammals, a process called X inactivation has evolved to
compensate for the extra X chromosome. In X inactivation, each cell ‘switches off’
one of its X chromosomes, chosen at random, to ensure the correct number of genes
are expressed, and to prevent abnormal development.
XCI is characterized by a cascade of molecular events beginning shortly after embryo
implantation, and is faithfully maintained throughout somatic cells in an organism.
This complex process starts with the cis-coating of the future inactive X chromosome
(Xi) by the long-non-coding RNA (lncRNA) Xist. Layers of chromatin and DNA
modifications catalyzed by proteins initially recruited by Xist RNA are then put in
place over several days during early development for stable transcriptional silencing
of each gene on the Xi. These modifications are associated with profound changes in
the 3D structure and location of the Xi, both processes depending on X-linked
lncRNA loci. The Xi adopts a bipartite structure consisting of two superdomains of
chromatin condensation separated by the lncRNA locus Dxz4, and the Xi visits the
nucleolus, a process facilitated by the lncRNA Firre
Frontiers | X Inactivation and Escape: Epigenetic and Structural Features
(frontiersin.org)
7. Parental DNA imprinting
Parental imprinting is a process that results in allele-specific differences in
transcription, DNA methylation, and DNA replication timing. Imprinting plays an
important role in development, and its deregulation can cause certain defined disease
states. The precise mechanism responsible for the imprint, or allele-specific behavior
of gene transcription, is still unclear; it is thought that modifications not involving the
DNA base sequence (therefore, epigenetic as opposed to genetic) have occurred
during the production of egg and sperm that mark genes according to parental origin.
People inherit two copies of their genes—one from their mother and one from their
father. Usually both copies of each gene are active, or “turned on,” in cells. In some
cases, however, only one of the two copies is normally turned on. Which copy is
active depends on the parent of origin: some genes are normally active only when
they are inherited from a person’s father; others are active only when inherited from a
person’s mother. This phenomenon is known as genomic imprinting.

In genes that undergo genomic imprinting, the parent of origin is often marked, or
“stamped,” on the gene during the formation of egg and sperm cells. This stamping
process, called methylation, is a chemical reaction that attaches small molecules
called methyl groups to certain segments of DNA. These molecules identify which
copy of a gene was inherited from the mother and which was inherited from the
father. The addition and removal of methyl groups can be used to control the activity
of genes.

Only a small percentage of all human genes undergo genomic imprinting. Researchers
are not yet certain why some genes are imprinted and others are not. They do know
that imprinted genes tend to cluster together in the same regions of chromosomes.
Two major clusters of imprinted genes have been identified in humans, one on the
short (p) arm of chromosome 11 (at position 11p15) and another on the long (q) arm
of chromosome 15 (in the region 15q11 to 15q13).

ECOGENETIC
1. Ecogenetic
Ecogenetics is a branch of genetics that studies genetic traits related to the
response to environmental substances.[1] Or, a contraction of ecological genetics, the
study of the relationship between a natural population and its genetic structure.
- Red blood cell conditions: There is a broad group of genetic diseases that result
in either producing or predisposing affected individuals to the development of
hemolytic anemias. These diseases include abnormal hemoglobin, inability to
manufacture one or the other of the peptide globin chains of the hemoglobin, and
deficiencies of the Embden-Meyerhoff monophosphate.
- Liver metabolism: Individuals lacking the ability to detoxify and excrete PCB's may
have a high risk of total liver failure in conjunction with certain ecological conditions.
- Cardiovascular diseases: The pathologic lesion of atherosclerosis is a plaque-like
substance that thickens the innermost and middle of the three layers of the artery
wall. The thickening of the intimal and medial layers results from the accumulation of
the proliferating smooth muscle cells that are encompassed by interstitial substances
such as collagen, elastin, glycosaminoglycans, and fibrin.
- Respiratory diseases: There are three genetically-based respiratory diseases that
can directly correspond with ecological functions and induce disease. These include
lung cancer and the upper and lower respiratory tract associated with a serum Ig A
deficiency.
2. Example of ecogenetic