Epigenetics

Question 1

4 key characterisitics of epigenetic phenomena

Answer 1

Different gene expression pattern inspite of identical genome

Inheritance through cell division, even through generations

Like a switch on/off

Erase-able (inter-convertible) (reversible) - therapeutic potential

Question 2

What does Waddington’s Landscape illustrate about epigenetics?

Answer 2

Each cell has initial potential to role down to one low energy state or another -

Stability is maintained because commitment pattern has rolled to energy minimum

Stable / low energy state

Question 3

What cofactor is needed for methylation of cytosine in CpG?

Answer 3

SAM

S-adenosyl methionine

Question 4

Who maintains epigenetic marks through somatic cell divisions?

Answer 4

Maintenance methyltransferase

Question 5

How does maintenance methyltransferase know to methylate?

Answer 5

Based on the CpG symmetry on complementary strand

Question 6

Does epigenetics enable things aside from DNA methylation gene silencing?

Answer 6

Yes, it also assists with packagin eukaryotic DNA into chromatin - via histone modificaiton

Question 7

Histone H3 modifications that affect gene expression - does it inhibit or repress?

Answer 7

Depending on the type of histone modification - it can do either

Repressive - usually methylate lysine

Acive - usually acetylate lysine

But the pattern dictates

Question 8

How is histone modification maintained during DNA replication?

Answer 8

Somehow the new strand can communicate with the old and re-establish histone marks by communicating with neighbor?

Question 9

When does inheritance of the chromatin state begin?

Answer 9

At DNA replication

S phase of cell cycle

Question 10

What is chromatin assembly ?

Answer 10

When new strand is made, you really only have 1/2 the available nucleasomes necessary for the two strands - so you have to synthesis 1/2 de novo (chromatin assembly) - these are naive and don’t have post-translational modificaiton state -

talk to the neighbors and convince them to similarly modified

Question 11

What could be a potential problem for maintaining an epigenetic state (DNA methylation / histone modification) when synthesizing new DNA?

Answer 11

DNA is half old half new
Histones half old half new

Histones have to convince new histones to be appropriately modified - but enzymes can do this :)

Question 12

If you give genetically comparable mothers different diets during gestation (one high methyl donor one low methyl donor) what will you see?

Answer 12

The gene primed for methylation is turned off in the mouse fed higher diet (because methylated) and not turned off in the mouse fed lower (unmethylated)

Question 13

Epigenetic changes can lead to a diversity of _________

Answer 13

stable differentiated cell types

Question 14

Imprinted genes

Answer 14

maternal and paternal alleles provide sex specific expression patterns - happens in gametes

Question 15

Epigenetic marks (3)

Answer 15

methylation
histone modifications
- (hetero and euchromatin)
X inactivation

Question 16

How can epigenetic mechanisms and inheritance occur outside nucleus?

Answer 16

Could be through protein structure (e.g. prion - CJD)

Could be trans-acting factors inherited in cytosol during cells division

Question 17

What happens (epigenetically) to tumor suppressor genes in cancer?

Answer 17

Their promoters are frequently methylated

Question 18

Histone deacetylases -

Answer 18

remove acetyl groups from lysine typically to silence genes

Question 19

So what two things work together to silence gene expression?

Answer 19

Histone deacetylase and DNA methylation

Question 20

How could we target cancer cells using epigenetics

Answer 20

DNA methyltransferase inhibitor
Histone deacetylase inhibitor

Removing the repression of TSG