Epigenetics

‘Epi’ – ‘genetics’

• ‘Epi’: On top of
• Definition:
The study of changes in organisms caused by modification of
gene expression rather than alteration of the genetic code
itself.
DNA
• How many cell types are in the human body?
• 50 Trillion cells, 200 different types
• But all have the SAME DNA.
 DNA structure within the nucleus
• There is about 2 m of DNA in
every nucleus in every cell in
your body.
• To fit in the nucleus it must be
tightly wound and compacted.
• The DNA wraps around a group
of proteins called a
nucleosomes, made up of 8
histone proteins.
• Histone proteins have ‘tails’
that can be chemically
modified in a few different
ways, such as methylation and
acetylation.
• DNA can also be methylated
directly on the cytosine base.
• All of these modifications are
considered epigenetics!
 Regulating the gene expression
Imagine your Each chromosome a Epigenetic marks are
Genome is a library separate book of similar to bookmarks that
in the nucleus instructions tell the cell what genes to
express or silence.

Gene
Epigenetic mark: On
Methylation
Epigenetic tags can act like
Off a traffic light system, genes
can be on, poised or off.
 The central dogma
DNA methylation, of its cytosine
base, controls how compacted the
DNA is, and therefore how accessible
to transcription machinery the DNA
is.

DNA methylation keeps higher order

regulation of which genes can be
expressed or silenced.

It is also is used to determine which

genes will be inherited from the
mother and which from the farther.
This is a process called X-inactivation.
 Epigenetic landscape: Waddington
Landscape

Cells differentiate along a Stem cell

pathway and cannot easily go
back or change to another
pathway. The hills along this

n o
ati
pathway that prevent this Progenitor cell

nti
differentiation change are ere
heavily influenced by
Diff

epigenetics.

Fully differentiated cell

Factors that can cause changes in epigenetics
Names some factors you think may have an affect on your epigenetics

Diet, exercise, pollution, sun exposure, smoking/toxins

and age are the main factors effecting epigenetics
 Heritable & imprinting
• Early development most epigenetics are de-methylated/ removed
but some specific ones are kept – this is called imprinting.
• Epigenetic ‘silencing’ ensures a gene is turned off. This is extremely important in female mammals to stop them
from having twice as many X-chromosome gene products as males.

Diet affecting epigenetics example:

Agouti mice – studied the imprinting of genes for hair colour and obesity. Both of these mice are from the same
mother but are fed different diets. When put on the same diet the appearance of the mouse on the left will
change to that of the mouse on the right.
 Age effecting epigenetics: Identical
twins
• Epigenetics are very similar,
almost identical in identical
twins
• But as people get older the
factors they are exposed to
are different
Age

• Causing changes to
their Epigenetics.
• These changes lead
to physical
differences that can
be more easily
studied using
identical twins.
The study of epigenetics
Epigenetics has a major influence over diseases such as cancer.
Therefore we need to study epigenetics to understand what is changing and how,
to improve healthy ageing.

This information can then be used to create therapies and even help early
detection of disease.

Why don’t you help out the scientists by joining our team at The Babraham
Institute, in the lab and helping us discover more about epigenetics?

(INSERT ESCAPE ROOM LINK)

Further discussion:
• Disease and epigenetics:
The first disease to be linked to epigenetics was cancer in 1983.

Another linked disease is Fragile X syndrome which affects 1 in 4,000 males and 1
in 8,000 females.

Why do you think males are more affected than females in this disease?
• Epigenetics in treatments:
Therapies for epigenetics are preferable as they do not require changing the DNA.
Chemicals can be used to naturally silence genes by methylating them or
preventing/removing methylation.

Caution should be used when using epigenetic therapies. Why do you think this is?
Question: Define histone acetylation and explain its role in gene expression regulation.
Answer: Histone acetylation involves the addition of acetyl groups to histone proteins, which neutralizes their
positive charge and loosens chromatin structure, allowing for increased access of transcriptional machinery to
DNA and thus promoting gene expression.
Question: What is the function of DNA methyltransferases in epigenetic regulation?
Answer: DNA methyltransferases (DNMTs) are enzymes responsible for adding methyl groups to cytosine
bases in DNA, leading to DNA methylation. They play a crucial role in gene silencing and the maintenance of
genomic stability.
Question: Explain the concept of epigenetic inheritance and provide an example.
Answer: Epigenetic inheritance refers to the transmission of epigenetic modifications from one generation to
the next without changes in the DNA sequence. An example is the transmission of DNA methylation patterns
during cell division and potentially across generations.
Question: What is the role of chromatin remodeling complexes in epigenetic regulation?
Answer: Chromatin remodeling complexes are protein complexes that alter chromatin structure by
repositioning, ejecting, or modifying histone proteins. They play a crucial role in regulating gene expression by
making DNA more accessible or inaccessible to transcription factors and other regulatory proteins.
Question: Describe the function of microRNAs (miRNAs) in post-transcriptional gene regulation.
Answer: MicroRNAs (miRNAs) are small non-coding RNAs that bind to target mRNAs, typically in the 3'
untranslated region (UTR), leading to mRNA degradation or translational repression, thereby regulating gene
expression at the post-transcriptional level.
Question: What is the significance of CpG islands in the mammalian genome?
Answer: CpG islands are regions of DNA rich in cytosine and guanine nucleotides, often found near
gene promoters. They are frequently unmethylated and play a crucial role in gene regulation by
influencing transcription initiation and chromatin structure.
Question: How do environmental factors such as diet and stress influence epigenetic modifications?
Answer: Environmental factors such as diet, stress, toxins, and lifestyle choices can influence
epigenetic modifications by altering DNA methylation patterns, histone modifications, and miRNA
expression, leading to changes in gene expression and phenotype.
Question: Define the term "epigenetic drift" and explain its implications for aging and disease.
Answer: Epigenetic drift refers to age-related changes in epigenetic modifications, including DNA
methylation and histone modifications. It can lead to alterations in gene expression patterns, genomic
instability, and an increased risk of age-related diseases such as cancer and neurodegenerative
disorders.
Question: How does RNA interference (RNAi) contribute to epigenetic regulation?
Answer: RNA interference (RNAi) involves the silencing of gene expression through the action of
small RNAs, such as siRNAs and miRNAs. These RNAs can target specific mRNAs for degradation
or translational repression, thereby modulating gene expression levels and contributing to epigenetic
regulation.
Question: What are the potential therapeutic applications of targeting epigenetic modifications?
Answer: Targeting epigenetic modifications holds promise for the treatment of various diseases,
including cancer, neurodegenerative disorders, and metabolic diseases. Epigenetic therapies aim to
reverse abnormal epigenetic changes associated with disease states and restore normal gene
expression patterns. Examples include DNA methyltransferase inhibitors and histone deacetylase
inhibitors for cancer treatment.