L11 - epigenetics and cancer Flashcards
How are epigenetic processes implicated in cancer?
Aberrant changes in chromatin modification that cause stable, heritable changes to g.e. profile
By regulating chromatin structure what can epigenetic mechanisms do?
- control accessibility of target genes to polymerases
- directly control biochemical activity of transcriptional machinery
TRUE OR FALSE
Epigenetics change the nucleotide sequence?
False
Can you have both acetylation and methylation?
No, they are competing reactions
What are some key features of acetylation?
Addition of acetyl groups but HATs. Can be added to different lysine groups, all activating - creates BS for TF with bromodomain - code reading
What are some key features of methylation?
Can be activation or repression of genes. Added with site specificity
What does methylation create binding sites for?
Repressors with chromodomain OR activators with PHD zinc finger domain
What is the significance of EZH2 in prostate cnacer?
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
What are nucleosomes?
Building blocks of chromatin. N-terminal tails are targetted for modification
What is the polycomb group?
Polycomb repressive complexes (PRC) are a group of proteins that can generate or recognise repressive chromatin modifications
What happens in cells in which EZH2 has been knocked out?
Cells cultured in matrigel - if invasive they will move through the holes. EZH2 overexp have invasive phenotype. EZH2 siRNA have a decreased invasive phenotype
What is chromosomal translocation?
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
What modification occurs in AML and ALL?
AML: MOZ (HAT) - CREBBP (HAT)
ALL: MLL (HMT) - CREBBP (HAT)
Fusion causes population of immortalised haem SC
What happens in mixed lineage leukaemia (MLL)?
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
