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Epigenetics:

• Genetics: the study of heritable changes in gene function


that occur with a change in the DNA sequence
• Epigenetics: the study of heritable changes in gene
function that occur without a change in DNA sequence.
• Changes in gene expression without changes to DNA sequence
passed on through cell division
• Study of the regulation of gene activity that is not dependent on
gene sequence
What is Epigenetics?
• Critical components for development and growth of cells
• Influence gene function/expression
• Epigenetic abnormalities are thought to be involved in
cancer, pediatric syndromes, contributing factors in
autoimmune diseases, aging…
• Diet and other environmental factors may be key
regulators of epigenetic processes
• Epigenetics can be defined as somatically heritable states
of gene expression resulting from changes in chromatin
structure without alterations in the DNA sequence
• Critical mechanisms :
• DNA methylation,
• Histone posttranslational modifications,
• Non-coding RNA, and
• Chromatin remodeling.
Multiple Components of Epigenetics
• Over the past decades, epigenetic studies mainly have
been focused on embryonic development, aging, and
cancer
• Presently, epigenetics is highlighted in many other fields,
such as inflammation, obesity, insulin resistance, type 2
diabetes mellitus, cardiovascular diseases,
neurodegenerative diseases, and immune diseases.
• Epigenetic modifications can be altered by
external or internal environmental factors and
have the ability to change gene expression,
• Epigenetics is now considered an important
mechanism in the unknown etiology of many
diseases.
• Induced epigenetic changes can be inherited during cell
division, resulting in permanent maintenance of the
acquired phenotype.
• Thus, epigenetics can provide a new framework for the
search for etiological factors in environment-associated
diseases as well as embryonic development and aging,
which are also known to be affected by many
environmental factors.
Epigenetic Mechanisms, Health
and Disease
Chromatin Structure Influences Gene
Expression

• Davis CD & Ross SA. Nutr Rev. 65:88-94, 2007.


Temporal Susceptibility of Epigenetic
Modulation
• Gametogenesis
• Preimplantation stage of embryogenesis
• Fetal and neonatal periods of development
• Puberty?
• Aging
• In the nutritional field, epigenetics is exceptionally
important, because nutrients and bioactive food
components can modify epigenetic phenomena and alter
the expression of genes at the transcriptional level.
• Folate, vitamin B-12, methionine, choline, and betaine
can affect DNA methylation and histone methylation
through altering 1-carbon metabolism.
• Two metabolites of 1-carbon metabolism can affect
methylation of DNA and histones
• Other water-soluble B vitamins like biotin, niacin, and
pantothenic acid also play important roles in histone
modifications
• Bioactive food components directly affect enzymes
involved in epigenetic mechanisms
• For instance, genistein and tea catechin affects DNA
methyl-transferases (Dnmt).
MECHANISM????
What is Epigenetics?
• Epigenetics is the study of inherited changes in
phenotype (appearance) or gene expression caused by
mechanisms other than changes in the underlying DNA
sequence.

• These changes may remain through cell divisions for


the remainder of the cell's life and may also last for multiple
generations.

• Changes in gene expression that do not involve


alterations in DNA base sequence
Epigenetic Modifications
•DNA Methylation

•Histone Modification (e.g. Acetylation, methylation)

•Non-coding RNAs (e.g. microRNA)

•All Regulate Gene Expression


Epigenetic Modifications
•DNA Methylation
•C-5 position of cytosine in CpG
dinucleotides (Islands)
Epigenetic Modification: Histone Modifications

- When histones are tagged, or acetylated, chromatin is open


and genes are potentially active;
- When histones are not chemically tagged, deacetylated, the
chromatin condenses and genes silenced.
Epigenetic Modification: Non-coding RNAs

A new mechanism for gene


regulation

• RNA which is not used for


making proteins (non-coding
RNA) can be cleaved and
used to inhibit protein-coding
RNAs

•siRNAs, microRNAs (~22


Nucleotides; fine tune gene
Expression)
Epigenetic
modification of DNA
Methylation is the gradual addition of
chemical units known as methyl groups to
genes, and as these groups accumulate, the
gene gradually shuts down.
DNA methylation is the addition of a methyl group to the
carbon-5 position of cytosine residues.
• Alterations in DNA methylation
are regarded as epigenetic and
not genetic changes, because
they do not materially affect the
genetic code.
DNA Methylation & the Epigenetic Code

Paula Vertino, Henry Stewart Talks


DNA Methylation & Histone Modifications
Form the Epigenetic Code

Paula Vertino, Henry Stewart Talks


Methylation of Cytosine in DNA
5-Methyl Cytosine in DNA
Cytosine Methylation Maintains
Inactive-Condensed Chromatin State
Transcription factors
RNA polymerase
Transcription Acetylation

DNA methyltransferase 5-methyl-C

Methyl-CpG Histone deacetylase


Binding proteins
and associated
co-repressors

Transcription blocked
Deacetylation
X

Chromatin compaction
Transcriptional silencing
5-Methyl Cytosine is Found in
Heterochromatic Regions

John Greally, Henry Stewart Talks


Structure & Epigenetics of
Euchromatin versus Heterochromatin

Me
Maintenance of
Cytosine Methylation
Passive Demethylation of
5-Methyl-Cytosine

Alex Meissner, Henry Stewart Talks


Establishment and Maintenance of
Cytosine Methylation

Alex Meissner, Henry Stewart Talks


Some DNA Methyl Transferases are Essential

Alex Meissner, Henry Stewart Talks


Methylated DNA from Zygote to Adult
DNA Methylation Differentiates Totipotent Embryonic
Stem Cells from Unipotent Adult Stem Cells
DNA Methylation Differentiates Totipotent Embryonic
Stem Cells from Unipotent Adult Stem Cells
DNA Methylation Differentiates Totipotent Embryonic
Stem Cells from Unipotent Adult Stem Cells
Differentiated Cells can
Become Totipotent
X Chromosome Inactivation:
CG Island Methylation
Only one X is active
Inactive X has unacetylated histone H4
Environment can Influence Epigenetic Changes
Summary of Epigenetic Gene Regulation
• Patterns of DNA methylation in adult cells parallels
cell fate, chromatin structure and gene activation.
• Most DNA methylation is removed at fertilization and
re-established during embryogenesis.
• Patterns of histone modifications parallel DNA
methylation.
• Methylated gene regions are genetically inactive,
highly condensed and special histone modifications.
• X chromosome inactivation in females is correlated
with extensive CG island methylation on one
chromosome, condensation, inactivation and Barr
body formation.
• Alterations in gene and CG island methylation
patterns are seen in aging and in cancer.
• Most CG islands are not methylated except for X
chromosome inactivation and tumor suppressors in
cancer.
MATURNUWUN