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Chronic Disease > Introduction to Epigenetics > Flashcards

Introduction to Epigenetics Flashcards

1
Q

Define Epigenetics.

A

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

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2
Q

How are epigenetic heritable?

A

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.

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3
Q

Why are epigenetic important for chronic disease?

A

Can be modified by the environment increasing risk in development

Can be modified pharmacologically which may be avenue in treatment

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4
Q

What are the epigenetic markers?

A

DNA methylation

Histone modification

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5
Q

What is DNA methylation?

A

Only common occurring covalent modification of DNA.

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6
Q

Where is DNA methylated.

A

5 position of the cytosine ring.

Anywhere else is considered DNA damage.

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7
Q

What is the enzyme which leads to DNA methylation?

A

DNMT1, 3a, 3b (DNA methyltransferase)

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8
Q

What is different about DNMT1?

A

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

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9
Q

What is the role of DNMT 3a and b?

A

These do initial methylation in early embryonic development.

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10
Q

What is s-Adenosyl methionine (SAM)?

A

A methyl donor

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11
Q

What are the sites at which methylation occurs at called?

A

CpG sites

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12
Q

How many CpG sites are methylated?

A

70%

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13
Q

Does the genome have a lot of CpG sites?

A

No.

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14
Q

What is special about CpG islands?

A

They are methylation free

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15
Q

When is DNA methylation important?

A

Imprinted genes

Repetitive elements

Tissue specific expression

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16
Q

Why is DNA methylation important?

A

Causes transcriptional repression when needed.

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17
Q

What kinds of histone modification is there?

A

Acetylation

Methylation

Phosphorylation

Ubiquitination

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18
Q

Why are histone modifications complicated?

A

Many types of modifications well as many areas for modification.

19
Q

Where does histone methylation occur when it is inactivating?

A

Lysine 9 and 27 on histone 3

20
Q

What location does methylation have the opposite effect?

A

Lysine 4 redidue on histone 3

21
Q

What is epigenetic drift?

A

Change in epigenetic overtime due to ageing or environment.

22
Q

Why does epigenetic drift happen?

A

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

Age-related CpG island methylation can occur.

23
Q

Why is CpG island methylation a problem?

A

Loss of regulation in cancer and other chronic disease.

24
Q

Can methylation predict age?

A

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

25
Q

What is biological age?

A

Susceptibility to chronic disease

26
Q

Which genes are considered family cancer genes/

A

MLH1 (breast) and BRCA1 (colorectal)

Switched off by hypermethylation.

27
Q

What was the issue with southern blots?

A

Radioactivity

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

28
Q

What is a bisulfide modification?

A

Changes a cytosine to a thymidine.

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

29
Q

What is a CIMP?

A

CpG island methylator phenotype

30
Q

Why are CIMPs important?

A

Genome wide methylation analysis

31
Q

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

A

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

32
Q

How can DNA methylation patterns be used on disease stratification?

A

Molecular subgrouping

Identification of tumour primary site

Choice of treatment

33
Q

Why is molecular subgrouping important?

A

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

34
Q

Why is the identification of primary cancer sites important?

A

Cancer treatment varies

Patients can present after cancer has already metastasised

Site specific treatment

35
Q

What is the involvement of DNA methylation on drug resistance?

A

Can help determine the therapeutic window for cancer treatment.

36
Q

What is MGMT?

A

O6-methylguanine-DNA methyltransferase

37
Q

What is the role of MGMT?

A

Repairs specifically 06methylGuanine.

Transfers a methyl group to the protein.

38
Q

What effect does MGMT have on temozolomide?

A

MGMT expression controls Temozolomide sensitivity

39
Q

How does methylation affect MGMT?

A

Loss of MGMT due to promoter methylation

40
Q

How can DNA methylation be target in cancer therapy?

A

Inhibiting DNA methylation

Reversing DNA methylation

41
Q

What kind of drugs and reverse DNA methylation?

A

5-azacytidine

2’deoxy-5-azacytidine

AML

42
Q

Why does reverse DNA methylation work in myodisplacia?

A

Reactivating tumour suppressors

Activate the immune system

43
Q

What kinds of epigenetic inhibitors prevent cancer?

A

HDACi

HATi

HMTi

Chronic Disease (15 decks)

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