Epigenetics

Question 1

Describe acetylation

Answer 1

Gene expression, euchromatin, open structure
Acetyl transferase
Histone deacetylases
+ve charged lysine has acetyl group added- neutralises charge
Less affinity for -vely charged DNA - weakens interactions

Question 2

Histone methylation

Answer 2

Gene silenced
Histone methyltransferase
Histone demethylase (KMT2A)
+ charges aa has methyl group added which increases + charge
Increases affinity for DNA- binds tighter

Question 3

Name 4 epigenetic mechanisms

Answer 3

DNA methylation
Histone modification
Short non coding RNA
Long non coding RNA

Question 4

Describe micro RNA mechanism

Answer 4

Interferes with expression at translation
Regulates translation of mRNA to aa
Degrades mRNA - binds 3’UTR mRNA and induces enzymatic degradation
MRNA specific

Question 5

Describe lncRNA mechanism

Answer 5

Interacts with chromatin
Regulates Histone modification- hetero- to EU- chromatin & vice versa
Cell type specific
Respond to environmental stimuli

Question 6

Name two results of hypermethylation in cancer

Answer 6

Silences TSG

causes microsatellite instability

Question 7

Name results of hypomethylation in cancers

Answer 7

Increase genomic instability
Re activation of transposable elements
Loss of imprinting
Favours chromosome instability/ rearrangements

Question 8

Name two cancers associated with hypomethylation and loss of imprinting

Answer 8

Wilms tumour

CRC/ lung/liver: loss control of IGFR causes increases of expression

Question 9

Name two types of epigenetic therapy

Answer 9

Targeting DNA methylation

Targeting Histone modification

Question 10

Describe DNA methylation based epigenetic therapy and an example of disease/drug

Answer 10

Acts like cytosine- incorporates into DNA at replication and inhibits DNMT enzymes from acting (methylating)
Re activates silenced gene
MDS: 5-azacytidine. / 5-aza-3’-deoxycytidine

Question 11

Describe Histone modification based epigenetic therapy and disease its associated with

Answer 11

Histone deacetylase inhibitors
Prevent removal of acetyl group from lysine- prevents gene from being silenced
Neurological/ neurodegenerative disease

Question 12

Describe DNA methylation

Answer 12

Gene silencing
DNA methyl transferase DNMT
Methyl group added to 5’cytosine in CpG Island
Physically inhibits binding of transcription factors
Attracts MBD methyl CpG domain binding proteins (MeCP2) they attract his tone deactylases