Introduction to Epigenetics

Question 1

Define Epigenetics.

Answer 1

Heritable changes in gene expression that are not a consequence of changes in DNA sequence

Question 2

How are epigenetic heritable?

Answer 2

In stem cells epigenetic not established so daughter cells can be any cell type.

In established cells the daughters inherit the epigenetics maintaining the tissues.

Question 3

Why are epigenetic important for chronic disease?

Answer 3

Can be modified by the environment increasing risk in development

Can be modified pharmacologically which may be avenue in treatment

Question 4

What are the epigenetic markers?

Answer 4

DNA methylation

Histone modification

Question 5

What is DNA methylation?

Answer 5

Only common occurring covalent modification of DNA.

Question 6

Where is DNA methylated.

Answer 6

5 position of the cytosine ring.

Anywhere else is considered DNA damage.

Question 7

What is the enzyme which leads to DNA methylation?

Answer 7

DNMT1, 3a, 3b (DNA methyltransferase)

Question 8

What is different about DNMT1?

Answer 8

It copies the methylation of the old strand onto a freshly translated one.

Question 9

What is the role of DNMT 3a and b?

Answer 9

These do initial methylation in early embryonic development.

Question 10

What is s-Adenosyl methionine (SAM)?

Answer 10

A methyl donor

Question 11

What are the sites at which methylation occurs at called?

Answer 11

CpG sites

Question 12

How many CpG sites are methylated?

Answer 12

70%

Question 13

Does the genome have a lot of CpG sites?

Answer 13

No.

Question 14

What is special about CpG islands?

Answer 14

They are methylation free

Question 15

When is DNA methylation important?

Answer 15

Imprinted genes

Repetitive elements

Tissue specific expression

Question 16

Why is DNA methylation important?

Answer 16

Causes transcriptional repression when needed.

Question 17

What kinds of histone modification is there?

Answer 17

Acetylation

Methylation

Phosphorylation

Ubiquitination

Question 18

Why are histone modifications complicated?

Answer 18

Many types of modifications well as many areas for modification.

Question 19

Where does histone methylation occur when it is inactivating?

Answer 19

Lysine 9 and 27 on histone 3

Question 20

What location does methylation have the opposite effect?

Answer 20

Lysine 4 redidue on histone 3

Question 21

What is epigenetic drift?

Answer 21

Change in epigenetic overtime due to ageing or environment.

Question 22

Why does epigenetic drift happen?

Answer 22

Patterns of DNA methylation are inherited between cell generations but not that efficiently.

Age-related CpG island methylation can occur.

Question 23

Why is CpG island methylation a problem?

Answer 23

Loss of regulation in cancer and other chronic disease.

Question 24

Can methylation predict age?

Answer 24

Yes can predict biological age can compare 353 CpG sites methylation to the age +/- 5 years.

Question 25

What is biological age?

Answer 25

Susceptibility to chronic disease

Question 26

Which genes are considered family cancer genes/

Answer 26

MLH1 (breast) and BRCA1 (colorectal) Switched off by hypermethylation.

Question 27

What was the issue with southern blots?

Answer 27

Radioactivity High volume of DNA required, this is was was used to study familial cancer cells.

Question 28

What is a bisulfide modification?

Answer 28

Changes a cytosine to a thymidine. Changes the DNA sequence, this helped up to look into the link between.

Question 29

What is a CIMP?

Answer 29

CpG island methylator phenotype

Question 30

Why are CIMPs important?

Answer 30

Genome wide methylation analysis

Question 31

Is DNA methylation the best technique for tumour suppressors which drive cancer?

Answer 31

No way more complicated than originally thought, 1000s of genes for tumour expressors

Question 32

How can DNA methylation patterns be used on disease stratification?

Answer 32

Molecular subgrouping Identification of tumour primary site Choice of treatment

Question 33

Why is molecular subgrouping important?

Answer 33

Can identify different sub groups for the same cancer and can be treated differently

Question 34

Why is the identification of primary cancer sites important?

Answer 34

Cancer treatment varies Patients can present after cancer has already metastasised Site specific treatment

Question 35

What is the involvement of DNA methylation on drug resistance?

Answer 35

Can help determine the therapeutic window for cancer treatment.

Question 36

What is MGMT?

Answer 36

O6-methylguanine-DNA methyltransferase

Question 37

What is the role of MGMT?

Answer 37

Repairs specifically 06methylGuanine. Transfers a methyl group to the protein.

Question 38

What effect does MGMT have on temozolomide?

Answer 38

MGMT expression controls Temozolomide sensitivity

Question 39

How does methylation affect MGMT?

Answer 39

Loss of MGMT due to promoter methylation

Question 40

How can DNA methylation be target in cancer therapy?

Answer 40

Inhibiting DNA methylation Reversing DNA methylation

Question 41

What kind of drugs and reverse DNA methylation?

Answer 41

5-azacytidine 2’deoxy-5-azacytidine AML

Question 42

Why does reverse DNA methylation work in myodisplacia?

Answer 42

Reactivating tumour suppressors Activate the immune system

Question 43

What kinds of epigenetic inhibitors prevent cancer?

Answer 43

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