Epigenetics

Question 1

What is epigenetics

Answer 1

genetic identity is the same but phenotypic identify makes us different. The way genes are expressed - are turned on or off - not to do with mutations

Question 2

What are genes

Answer 2

segments of DNA that provide instructions to make proteins

Question 3

What does the promoter region of a gene do

Answer 3

it is the start of the gene that defines which are turned on or off

Question 4

What is methylation

Answer 4

methyl group binds to histone tails or DNA

methyl group causes the DNA to be condensed so genes are turned off

transcription factors can’t get in = gene silencing

Question 5

Why is methylation of TSG bad

Answer 5

tumour suppressor genes can’t be expressed which can lead to cancer growth

Question 6

What is acetylation

Answer 6

the histones are further apart and the DNA is more loose - the gene is exposed and turned on this allows transcription to take place

TSG can be expressed

Question 7

Name 3 enzymes that carry out DNA methylation of histones and their role

Answer 7

1. DNMT1 - maintenance of methylation
2. DNMT3A - starts methylation
3. DNMT3B - starts methylation

Question 8

Describe the process of DNA methylation

Answer 8

DNMT enzyme adds methyl group to cytosine residue by binding directly to the DNA or the histone tails

Question 9

How are the promoter regions of TSG’s different in normal cells to cancer cells?

Answer 9

Normal: Promoter regions of tumour suppressor genes are not methylated (off) so the gene can be transcribed and promoted.

In cancer: the promoter region is heavily methylated and prevents the expression of tumour suppressor genes and contributes to cancer

Question 10

What are two types of epigenetic drugs that target major enzymes

Answer 10

• DNMT inhibitors
• HDAC inhibitors

Question 11

What is a type of epigenetic drug that targets specific proteins

Answer 11

EZH2 inhibitors

Question 12

Describe the mechanism of action of 5-azacytidine

Answer 12

it is a DNMT1 inhibitor - it stops the methylation process of the promoter, this allows for tumour suppressor gene to be expressed and cancer cells are reversed

Question 13

What are 3 clinical outcomes of using 5-azacytidine

Answer 13

1. decreases methylation
2. fewer grade 4 toxicities
3. Increases patient survival

Question 14

What is the MoA of HDAC inhibitors

Answer 14

histone deacetylase wraps the DNA to prevent tumour suppressor genes being exposed

histone deacetylase inhibitors increase acetylation of histones to allow TSGs to be transcribed and expressed

Question 15

What type of epigenetic drug is Chidamide and what cancer does it treat

Answer 15

HDAC inhibitor used to treat breast cancer

Question 16

How does EZH2 cause methylation

Answer 16

EZH2 is a catalytic component of PRC2

PRC2 is a chromatin modifying enzyme that catalyses trimethylation (me3) at histone 3 (H3) and lysine 27 (k27)
this condenses the DNA and silences tumour suppressor genes - promoting proliferation, invasion and drug resistance of cancer cells

Question 17

Describe the mechanism of action of Tazemetostat and what cancer is it used for

Answer 17

It is a EZH2 inhibitor

It is used for follicular lymphoma

EZH2 in follicular lymphoma is overexpressed and silences TSG CDK1a/2a which leads to proliferation and cancer cell growth

Tazemetostat inhibits EZH2 and allows for CDK1a/2a to be expressed

Question 18

What are common side effects of Tazemetostat

Answer 18

• constipation
• low energy
• nausea
• vomiting

Question 19

What are rare side effects of Tazemetostat

Answer 19

• sores
• ulcers
• swollen glands