L11 - epigenetics and cancer

Question 1

How are epigenetic processes implicated in cancer?

Answer 1

Aberrant changes in chromatin modification that cause stable, heritable changes to g.e. profile

Question 2

By regulating chromatin structure what can epigenetic mechanisms do?

Answer 2

• control accessibility of target genes to polymerases

- directly control biochemical activity of transcriptional machinery

Question 3

TRUE OR FALSE

Epigenetics change the nucleotide sequence?

Answer 3

False

Question 4

Can you have both acetylation and methylation?

Answer 4

No, they are competing reactions

Question 5

What are some key features of acetylation?

Answer 5

Addition of acetyl groups but HATs. Can be added to different lysine groups, all activating - creates BS for TF with bromodomain - code reading

Question 6

What are some key features of methylation?

Answer 6

Can be activation or repression of genes. Added with site specificity

Question 7

What does methylation create binding sites for?

Answer 7

Repressors with chromodomain OR activators with PHD zinc finger domain

Question 8

What is the significance of EZH2 in prostate cnacer?

Answer 8

It is often overexpressed. The role of EZH2 is to generate or recognise repressive chromatin modifications. It’s overexpression is accompanied by an increase in H3K27 methylation (an inactivating modification). It promotes the proliferation and invasiveness of prostate cancer by decrease trsc of many genes in the cancer cells

Question 9

What are nucleosomes?

Answer 9

Building blocks of chromatin. N-terminal tails are targetted for modification

Question 10

What is the polycomb group?

Answer 10

Polycomb repressive complexes (PRC) are a group of proteins that can generate or recognise repressive chromatin modifications

Question 11

What happens in cells in which EZH2 has been knocked out?

Answer 11

Cells cultured in matrigel - if invasive they will move through the holes. EZH2 overexp have invasive phenotype. EZH2 siRNA have a decreased invasive phenotype

Question 12

What is chromosomal translocation?

Answer 12

Movement of one sections of a chr. to another
Bad if it between non-homologus chr.
Causes disruption of genes or fusion of new genes

Question 13

What modification occurs in AML and ALL?

Answer 13

AML: MOZ (HAT) - CREBBP (HAT)
ALL: MLL (HMT) - CREBBP (HAT)
Fusion causes population of immortalised haem SC

Question 14

What happens in mixed lineage leukaemia (MLL)?

Answer 14

Translocation involving histone readers and writers
MLL deletes PHD domain, trsc act region and H3K4 methyltransferase domain - leave fusion pt with repressor domain. Normally the protein would allow the trsc activation of chromatin. The mutant protein acts as a dominant -ve inhibitor of wt pt