Epigenetics Flashcards
What is epigenetics
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
What are genes
segments of DNA that provide instructions to make proteins
What does the promoter region of a gene do
it is the start of the gene that defines which are turned on or off
What is methylation
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
Why is methylation of TSG bad
tumour suppressor genes can’t be expressed which can lead to cancer growth
What is acetylation
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
Name 3 enzymes that carry out DNA methylation of histones and their role
- DNMT1 - maintenance of methylation
- DNMT3A - starts methylation
- DNMT3B - starts methylation
Describe the process of DNA methylation
DNMT enzyme adds methyl group to cytosine residue by binding directly to the DNA or the histone tails
How are the promoter regions of TSG’s different in normal cells to cancer cells?
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
What are two types of epigenetic drugs that target major enzymes
- DNMT inhibitors
- HDAC inhibitors
What is a type of epigenetic drug that targets specific proteins
EZH2 inhibitors
Describe the mechanism of action of 5-azacytidine
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
What are 3 clinical outcomes of using 5-azacytidine
- decreases methylation
- fewer grade 4 toxicities
- Increases patient survival
What is the MoA of HDAC inhibitors
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
What type of epigenetic drug is Chidamide and what cancer does it treat
HDAC inhibitor used to treat breast cancer
How does EZH2 cause methylation
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
Describe the mechanism of action of Tazemetostat and what cancer is it used for
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
What are common side effects of Tazemetostat
- constipation
- low energy
- nausea
- vomiting
What are rare side effects of Tazemetostat
- sores
- ulcers
- swollen glands
