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Genetics Of Complex Disease > Epigenetics 1 > Flashcards

Epigenetics 1 Flashcards

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1
Q

What is epi genetics

A

Heritable changes in phenotype or gene expression caused by mechanisms other than changing dna sequence

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2
Q

As the organism gets more complex why is there less protein coding sequences

A

Need more regulatory dna

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3
Q

What is regulatory dna

A

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

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4
Q

What affects tf action

A

Epi genetics
Nuclear import and export
Cofactors
Their own exp

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5
Q

Explain the packaging of dna

A

Dna wraps around histone protein octamer which is 2x h2a 2b dimer and 1 h3 h4 dimer

= form nucleosomes

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6
Q

What holds the dna to histones

A

Hydrophobic and salt linkage as the positive lysine and arginine neutralises negative backbone on dna

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7
Q

What 2 types of chromatin are there

A

Heterochromatin - txn off

Euchromatin

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8
Q

Which residues are acetylated to cause more gene expression/ opens up dna as it adds a negative charge

A

Lysine

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9
Q

Give an example of a HAT/ coactivator complex with intrinsic hat activity

A

Cbp/p300

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10
Q

Which other coactivation factor can act in complex with an 300/cbp as it has HAT activity

A

PCAF

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11
Q

Which types of proteins are recruited to acrtylated lysine residues as readers

A

Bromodomain containing proteins

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12
Q

Which enzymes are targeted through cancer inhibitors and why

A

HDACs, because they will stop txn of many important genes like tumour suppressors

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13
Q

What has hypoacettlstion eg through increased HDAC exp been linked to in neurodegeneration/ageing

A

Reduced exp of genes important for synaptic plasticity (important for learning and memory)

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14
Q

How has HDAC overexp linked to invasive ness of carcinomas

A

HDAC 1 and 2 cause hypoacetylation of the ecadherin promoter so no barrier to metastasis

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15
Q

What can bromodomain binding do

A

Cause more acetylation of adjacent nucleosomes if binds to hat complexes

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16
Q

What has the combination of a bromodomain inhibitor and a hat inhibitor been used for

A

To block the expression of pro-oncogenes in cancers (see fr)

17
Q

What sort of residues does histone methylation done on

A

Basic eg lysine

18
Q

What are their readers

A

Methyl binding domain containing proteins eg phd fingers

19
Q

What do these proteins act as

A

Co repressors

20
Q

What is a hkmt example which is over expressed in many cancers (oncogenic)

A

Ezh2

21
Q

What happens to heterochromstin as you age

A

It is being reduced constantly due to expression of more hkmt like ezh2

22
Q

What does this imply

A

Ageing might be because certain genes that were not as expressed before are now

23
Q

Why is studying cpg methylation important

A

Only one which can be inherited

24
Q

What are the writers readers and erases

A

Dnmts

Read by MBD proteins or cg binding proteins if unmethylated

Tet proteins remove it

25
Q

Where are cpg islands usually found

A

5’ utr or exon 1 of fene

26
Q

Give an example where hypermethtlstion of a dna repair gene occurs in cancers

A

Mgmt and brca1

27
Q

What also gets hyper methylated which increases mdm2 degradation of p53

A

P14 arf

28
Q

Which gene which can cause apoptosis of cells eg cancer cells via ifny is hypermethylated

A

Dapk

29
Q

Give an example of how a protein/a phd finger binds to unmethylated cpgs to stimulate methylation

A

Cfp1/cxxc1 recruits set1 complex which stimulates h3k4 methylation

30
Q

Which leukaemia in the other lecture showed a variant in cfp1/cxxc1, suggesting there are epi genetics involved

A

Cll

31
Q

Which mbd is mutated in Rett syndrome which is a epi genetic neurological disorder

A

Mecp2

32
Q

Is mecp2 a coactivator or a corepressor

A

Can act as a coactivator of exp if in complex with eg cbp

Also a corepressor of exp if in complex with eg sin3a

33
Q

Mutations in the RTD of mecp2 cause what

A

Lack of corepressor activity as it can’t interact with repressor complexes

34
Q

Which mutation found in mbd which completely stops mecp2 from binding methylated cpgs

A

T158 position

35
Q

What sort of symptoms are these mutations causing in Rett syndrome

A

Microcephaly, impaired social interactions, learning and language

36
Q

Give another example of an epi genetic disorder

A

ATR-x syndrome which also causes a thalassemia

Genetics Of Complex Disease (17 decks)

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