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Epigenetics
Student name: Ahmed Al-jammal
Prof. Dr. Mohamad shatnawi
1
History of epigenetics
- The term epigenetics in its contemporary usage appeared
in the 1990s
- It was used with slightly different meanings
- In 2008 a special concept was reached in epigenetic
inheritance Cold Spring Harbor Laboratory.
- British embryologist Conrad Waddington coined the term
epigenetics in 1942 by analogy to the term phenogenetics
coined by Valentine Hecker.
History of epigenetics
- When Waddington coined the term the physical nature of genes
and their role in heredity was unknown Instead he used it as a
conceptual model for how genetic components might interact with
the environment to produce a phenotype.
- Nowadays Waddington's idea of ​​an 'epigenetic landscape' is
firmly established within the context of the system dynamics
approach to the study of cell fate.
What is Epigenetics?
A study that investigates alterations to gene expression or phenotype in
an organism that occur without changing the nucleotide sequence of a
gene (DNA).
What is Epigenetics?
Epigenetic inheritance explains the manufacture of proteins that
distinguish a particular cell from other cells
-For example: nerve cells make proteins that differ from those made by
other cells in the body although all human body cells have the same
sequence of nucleotides in the DNA molecule.
There is a relationship between Epigenetics and
gene expression:
Gene expression can be altered
as follows:
1- active gene That is, activating the gene in
order to build proteins through the process of
transcription and translation
2- silent gene Inhibiting the gene and
preventing the transcription and translation
process, so the protein building process does
not occur
The DNA will not
transcription and
translation
The DNA will
transcription and
translation
There are basic molecular epigenetic mechanisms
1- Histone acetylation and deacetylation:
- Histone acetylation: histone acetyltransferase (HATs) adds acetyl groups (Ac) onto histone tails
which results in a nucleosome opening thus allowing for transcription factors to access DNA and
initiate gene transcription.
- Histone deacetylation: histone deacetylases (HDACs) remove acetyl groups (Ac) from the histone
tails, leading to a closed chromatin structure.
 Acetylation removes the positive charge on the
histones thereby decreasing the interaction of the
N termini of histones (Lysine) with the negatively
charged phosphate groups of (DNA).
 As a consequence the condensed chromatin is
transformed into a more relaxed structure that is
associated with greater levels of
gene transcription.
 This relaxation can be reversed by
deacetylation catalyzed by HDAC activity.
 Relaxed transcriptionally active DNA is referred to
as euchromatin. More condensed (tightly packed)
DNA is referred to as heterochromatin
Condensation can be brought about by processes
including deacetylation and methylation
2- DNA methylation
It involves adding a methyl group to:
 the fifth position of the pyrimidine ring of cytosine, generating 5-methylcytosine (5meC)
 the number-6 nitrogen of the purine ring of adenine
NOTE: Methylation usually occurs at the gene promoter and typically inhibits gene
transcription ,this change can be inherited through cell differentiation, and it is related to the
pathogenesis of various diseases
DNA methylation constitutes 2 processes
1. De novo methylation
2. 5-meC recognition
De novo methylation
is a process by which the addition of methyl groups to unmethylated DNA takes
place at specific CpG sites
Normally CpG sites are unmethylated and DNA methylation occurs in these sites
frequently.
CpG sites are the specific regions of DNA in which cytosine nucleotide is
followed by a guanine nucleotide in the linear sequence of bases along its 5′ → 3′
direction.
De novo methylation is catalyzed by two different methylates: DNMT3A and
DNMT3B.
5-Methylcytosine (5mC) is an important epigenetic modification that serves
as a marker for gene expression X-chromosome inactivation, and
transposon silencing, among other developmental processes
5-meC recognition
3- Micro-RNAs
• Are small noncoding RNAs approximately 18-25 nucleotides in length now recognized as one of the
major regulatory gene families in eukaryotes
• MicroRNAs are transcribed by RNA polymerases II and III
• The regulatory functions of microRNAs are accomplished through the RNA-induced silencing
complex (RISC)
• MicroRNA assembles into RISC, activating the complex to target messenger RNA (mRNA)
specified by the microRNA
• This will either lead to degradation of mRNA strand
Study the effect of methyl group on rats
• Two groups of pregnant rat mothers were brought, both carrying embryos
with homozygous genotype (AA) Then a different diet was established for
both mother mice:
The first group: the diet of the mothers in this group contained folic acid, which
is a source of a methyl group so the resulting mice had brown fur and were not
obese (normal).
The second group: the diet was devoid of folic acid so the
resulting mice had yellow fur, were obese, and were infected
with other diseases.
Conclusion: The scientists explained this (experiment) by saying
that the methyl group contained in the diet of the mice of the first
group represents a factor of epigenetic inheritance.
Epigenetic explains the difference in traits between identical
twins as follows:
One of the twins may suffer from certain diseases that the other does not
suffer from
One may become a sporter and the other a painter
They may differ in personal characteristics, such as one being shy,
unlike the other
It is true that they carry the same nucleotide arrangement in the
DNA molecule, but the gene expression of each of them differs
because:
1- They may differ in diet
2- They may differ in physical and social activities
3- They may differ in medical care
4- There is an association of epigenetic factors with one of them that
differ from those associated with the other at any stage of their lives
Some studies have shown that the older a person gets, the more
differences appear in epigenetic factors between identical twins.
epigenetics symptoms and disease
Epigenetic inheritance has created a scientific precedent with regard
to explaining the causes of cancer
Epigenetic factors may affect tumor suppressor genes, causing them to
become inactive (silent), which leads to the spread of tumors.
epigenetics symptoms and disease
• Epigenetics is an inheritable phenomenon that affects gene expression without base pair
changes.
• Epigenetic phenomena include DNA methylation, histone modifications, and chromatin
remodeling.
• Chromatin is quite dynamic and is much more than a neutral system for packaging and
condensing genomic DNA, it is a critical player in controlling the accessibility of DNA for
transcription.
• Modifications of chromatin structure can give rise to a variety of epigenetic effects.
• Due to its reversible character, epigenetics is now considered an attractive field of nutritional
intervention.
Conclusion
• During our lifetime, nutrients can modify physiologic and pathologic processes through epigenetic
mechanisms that are critical for gene expression (summarized in Table 1).
• Modulation of these processes through diet or specific nutrients may prevent diseases and maintain health
However, it is very hard to delineate the precise effect of nutrients or bioactive food components on each
epigenetic modulation and their associations with physiologic and pathologic processes in our body,
because the nutrients also interact with genes, other nutrients, and other lifestyle factors.
Thank you

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epigenetics.pptx

  • 1. Epigenetics Student name: Ahmed Al-jammal Prof. Dr. Mohamad shatnawi 1
  • 2. History of epigenetics - The term epigenetics in its contemporary usage appeared in the 1990s - It was used with slightly different meanings - In 2008 a special concept was reached in epigenetic inheritance Cold Spring Harbor Laboratory. - British embryologist Conrad Waddington coined the term epigenetics in 1942 by analogy to the term phenogenetics coined by Valentine Hecker.
  • 3. History of epigenetics - When Waddington coined the term the physical nature of genes and their role in heredity was unknown Instead he used it as a conceptual model for how genetic components might interact with the environment to produce a phenotype. - Nowadays Waddington's idea of ​​an 'epigenetic landscape' is firmly established within the context of the system dynamics approach to the study of cell fate.
  • 4. What is Epigenetics? A study that investigates alterations to gene expression or phenotype in an organism that occur without changing the nucleotide sequence of a gene (DNA).
  • 5. What is Epigenetics? Epigenetic inheritance explains the manufacture of proteins that distinguish a particular cell from other cells -For example: nerve cells make proteins that differ from those made by other cells in the body although all human body cells have the same sequence of nucleotides in the DNA molecule.
  • 6. There is a relationship between Epigenetics and gene expression: Gene expression can be altered as follows: 1- active gene That is, activating the gene in order to build proteins through the process of transcription and translation 2- silent gene Inhibiting the gene and preventing the transcription and translation process, so the protein building process does not occur
  • 7. The DNA will not transcription and translation The DNA will transcription and translation
  • 8. There are basic molecular epigenetic mechanisms
  • 9. 1- Histone acetylation and deacetylation: - Histone acetylation: histone acetyltransferase (HATs) adds acetyl groups (Ac) onto histone tails which results in a nucleosome opening thus allowing for transcription factors to access DNA and initiate gene transcription. - Histone deacetylation: histone deacetylases (HDACs) remove acetyl groups (Ac) from the histone tails, leading to a closed chromatin structure.
  • 10.  Acetylation removes the positive charge on the histones thereby decreasing the interaction of the N termini of histones (Lysine) with the negatively charged phosphate groups of (DNA).  As a consequence the condensed chromatin is transformed into a more relaxed structure that is associated with greater levels of gene transcription.  This relaxation can be reversed by deacetylation catalyzed by HDAC activity.  Relaxed transcriptionally active DNA is referred to as euchromatin. More condensed (tightly packed) DNA is referred to as heterochromatin Condensation can be brought about by processes including deacetylation and methylation
  • 11. 2- DNA methylation It involves adding a methyl group to:  the fifth position of the pyrimidine ring of cytosine, generating 5-methylcytosine (5meC)  the number-6 nitrogen of the purine ring of adenine NOTE: Methylation usually occurs at the gene promoter and typically inhibits gene transcription ,this change can be inherited through cell differentiation, and it is related to the pathogenesis of various diseases
  • 12.
  • 13. DNA methylation constitutes 2 processes 1. De novo methylation 2. 5-meC recognition
  • 14. De novo methylation is a process by which the addition of methyl groups to unmethylated DNA takes place at specific CpG sites Normally CpG sites are unmethylated and DNA methylation occurs in these sites frequently. CpG sites are the specific regions of DNA in which cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5′ → 3′ direction. De novo methylation is catalyzed by two different methylates: DNMT3A and DNMT3B.
  • 15. 5-Methylcytosine (5mC) is an important epigenetic modification that serves as a marker for gene expression X-chromosome inactivation, and transposon silencing, among other developmental processes 5-meC recognition
  • 16.
  • 17. 3- Micro-RNAs • Are small noncoding RNAs approximately 18-25 nucleotides in length now recognized as one of the major regulatory gene families in eukaryotes • MicroRNAs are transcribed by RNA polymerases II and III • The regulatory functions of microRNAs are accomplished through the RNA-induced silencing complex (RISC) • MicroRNA assembles into RISC, activating the complex to target messenger RNA (mRNA) specified by the microRNA • This will either lead to degradation of mRNA strand
  • 18.
  • 19. Study the effect of methyl group on rats • Two groups of pregnant rat mothers were brought, both carrying embryos with homozygous genotype (AA) Then a different diet was established for both mother mice: The first group: the diet of the mothers in this group contained folic acid, which is a source of a methyl group so the resulting mice had brown fur and were not obese (normal).
  • 20. The second group: the diet was devoid of folic acid so the resulting mice had yellow fur, were obese, and were infected with other diseases.
  • 21. Conclusion: The scientists explained this (experiment) by saying that the methyl group contained in the diet of the mice of the first group represents a factor of epigenetic inheritance.
  • 22. Epigenetic explains the difference in traits between identical twins as follows: One of the twins may suffer from certain diseases that the other does not suffer from One may become a sporter and the other a painter They may differ in personal characteristics, such as one being shy, unlike the other
  • 23. It is true that they carry the same nucleotide arrangement in the DNA molecule, but the gene expression of each of them differs because: 1- They may differ in diet 2- They may differ in physical and social activities 3- They may differ in medical care 4- There is an association of epigenetic factors with one of them that differ from those associated with the other at any stage of their lives
  • 24. Some studies have shown that the older a person gets, the more differences appear in epigenetic factors between identical twins.
  • 26. Epigenetic inheritance has created a scientific precedent with regard to explaining the causes of cancer Epigenetic factors may affect tumor suppressor genes, causing them to become inactive (silent), which leads to the spread of tumors.
  • 27.
  • 29.
  • 30.
  • 31. • Epigenetics is an inheritable phenomenon that affects gene expression without base pair changes. • Epigenetic phenomena include DNA methylation, histone modifications, and chromatin remodeling. • Chromatin is quite dynamic and is much more than a neutral system for packaging and condensing genomic DNA, it is a critical player in controlling the accessibility of DNA for transcription. • Modifications of chromatin structure can give rise to a variety of epigenetic effects. • Due to its reversible character, epigenetics is now considered an attractive field of nutritional intervention. Conclusion
  • 32. • During our lifetime, nutrients can modify physiologic and pathologic processes through epigenetic mechanisms that are critical for gene expression (summarized in Table 1). • Modulation of these processes through diet or specific nutrients may prevent diseases and maintain health However, it is very hard to delineate the precise effect of nutrients or bioactive food components on each epigenetic modulation and their associations with physiologic and pathologic processes in our body, because the nutrients also interact with genes, other nutrients, and other lifestyle factors.
  • 33.
  • 34.
  • 35.