Epigenetics and cancer Flashcards
(28 cards)
Define epigenetics.
Meiotically and mitotically heritable changes in the gene expresion that are not coded by the sequence itself.
How much DNA is wrapped around an octomer?
146 bp are wrapped around twice.
What are nucleosome remodelling enzymes?
Large (2 kDa) protein complexes, which in an ATP dependant manor reposition nucleosomes to expose different sections of DNA. This are not sequence specific so need to be recuited by other proteins like transcription factors. The families are SWI/SNF and ISWI.
How do histone tails become acetylated and what is the effect of this?
Lysine residues are neutrised by the addtion of a acetyl group and so does not interact with negative DNA as well and the chromatin structure opens. Additionally acetylated lysine group provide interacting sites for specific proteins. HATS add the acetyl group using acetyl-coenzyme A as a donor. HDAC remove the acetyl groups.
Which drugs inhibit HDACs?
trichostatin A, butyrate.
Who do HATS and HDAC get to DNA?
They are often recruited by transcription factors. HATS are not sequence specific.
Give three examples of HATS.
Gcn5, PCAF and p300/CBP.
What do acetylated lysine groups recruit?
Proteins which bromodomains including more HATs like p300/CBP. this pull in more proteins. Also nucleosome remodelling enzymes.
How does acetylated lysine marks directly lead to active transcription of genes.?
They recruit bromodomain proteins including p300/CBP which then recruited the mediator complex and basal transcription factors which act as a bridge to the recruited RNA Pol II which is then phosphorylated at the C-terminal domain and becomes active.
How are lysine residues of histone tails methylated?
histone methyl transferases (HMTs) add methyl groups from the donor S-adenosyl methionine to lysines to even mono- di- or tri-methylate. Demethylases remove the methyl groups.
Which lysines of H3 tails are active when methylated?
K4 (K39 and K79)
Which lysines of H3 tail are repressive when methylated?
K9 and K27.
Which HMT methylates K4?
MLL
Which HMT methylates K9?
Suv39
Which HMT methylates K27?
PRC2.
What is K27 methylation premeraly involved in
The silencing of genes in stem cell differentiation.
What is K9 methylation primarily involved in?
The constitutive condensing of DNA at e.g. centromers or telomeres.
What binds H3K9me?
HP1 (important in condensing chromation)
What binds H3K27me?
PCR1.
What is PRC2?
A HMT, contains EZH2 one which has a SET domain that carries out the methylation. It also contains the associated proteins SUZ12 and EED.
What does PRC1 do?
Binds H3K27me with polycomb ring fingers and ubiquitinates H2AK119 residue.
Which enzyme copied the DNA methylation pattern onto the new palamdromic strand after DNA replication.
DNMT1 and others a bit like it.
Describe the feedback mechanism loop which allows repressive chromatin to spread.
Me-CpG is bound by MBD proteins. These recuites HDAC and HMTS inculing Suv39 which methylates H3K9. H3K9me is then able to recruit HP1 leading to transcriptional silencing. Suv39 also recruits DNMTs to futher methylate CpGs and finish the loop.
How many promoter regions are CpG islands and are the generally methylated or unmethylated?
60% and unmethylated, mostly remain unmethylated even when not expressed.
