Epigenetics 1 Flashcards
What is epi genetics
Heritable changes in phenotype or gene expression caused by mechanisms other than changing dna sequence
As the organism gets more complex why is there less protein coding sequences
Need more regulatory dna
What is regulatory dna
Sequence usually before the gene which allows either increased or reduced exp of the gene
Ie where enhancers and silencers are and promoter with tf
What affects tf action
Epi genetics
Nuclear import and export
Cofactors
Their own exp
Explain the packaging of dna
Dna wraps around histone protein octamer which is 2x h2a 2b dimer and 1 h3 h4 dimer
= form nucleosomes
What holds the dna to histones
Hydrophobic and salt linkage as the positive lysine and arginine neutralises negative backbone on dna
What 2 types of chromatin are there
Heterochromatin - txn off
Euchromatin
Which residues are acetylated to cause more gene expression/ opens up dna as it adds a negative charge
Lysine
Give an example of a HAT/ coactivator complex with intrinsic hat activity
Cbp/p300
Which other coactivation factor can act in complex with an 300/cbp as it has HAT activity
PCAF
Which types of proteins are recruited to acrtylated lysine residues as readers
Bromodomain containing proteins
Which enzymes are targeted through cancer inhibitors and why
HDACs, because they will stop txn of many important genes like tumour suppressors
What has hypoacettlstion eg through increased HDAC exp been linked to in neurodegeneration/ageing
Reduced exp of genes important for synaptic plasticity (important for learning and memory)
How has HDAC overexp linked to invasive ness of carcinomas
HDAC 1 and 2 cause hypoacetylation of the ecadherin promoter so no barrier to metastasis
What can bromodomain binding do
Cause more acetylation of adjacent nucleosomes if binds to hat complexes
What has the combination of a bromodomain inhibitor and a hat inhibitor been used for
To block the expression of pro-oncogenes in cancers (see fr)
What sort of residues does histone methylation done on
Basic eg lysine
What are their readers
Methyl binding domain containing proteins eg phd fingers
What do these proteins act as
Co repressors
What is a hkmt example which is over expressed in many cancers (oncogenic)
Ezh2
What happens to heterochromstin as you age
It is being reduced constantly due to expression of more hkmt like ezh2
What does this imply
Ageing might be because certain genes that were not as expressed before are now
Why is studying cpg methylation important
Only one which can be inherited
What are the writers readers and erases
Dnmts
Read by MBD proteins or cg binding proteins if unmethylated
Tet proteins remove it
Where are cpg islands usually found
5’ utr or exon 1 of fene
Give an example where hypermethtlstion of a dna repair gene occurs in cancers
Mgmt and brca1
What also gets hyper methylated which increases mdm2 degradation of p53
P14 arf
Which gene which can cause apoptosis of cells eg cancer cells via ifny is hypermethylated
Dapk
Give an example of how a protein/a phd finger binds to unmethylated cpgs to stimulate methylation
Cfp1/cxxc1 recruits set1 complex which stimulates h3k4 methylation
Which leukaemia in the other lecture showed a variant in cfp1/cxxc1, suggesting there are epi genetics involved
Cll
Which mbd is mutated in Rett syndrome which is a epi genetic neurological disorder
Mecp2
Is mecp2 a coactivator or a corepressor
Can act as a coactivator of exp if in complex with eg cbp
Also a corepressor of exp if in complex with eg sin3a
Mutations in the RTD of mecp2 cause what
Lack of corepressor activity as it can’t interact with repressor complexes
Which mutation found in mbd which completely stops mecp2 from binding methylated cpgs
T158 position
What sort of symptoms are these mutations causing in Rett syndrome
Microcephaly, impaired social interactions, learning and language
Give another example of an epi genetic disorder
ATR-x syndrome which also causes a thalassemia
