Epigenetic p53

Question 1

What is epigenetic?

Answer 1

The study of changes in an organism which causes changes in gene expression but no changes in the genetic code

Question 2

What do human cancer cells undergo to differentiate?

Answer 2

Genome remodeling and genome reprogramming

Question 3

What happens in regards to p53 in cancer?

Answer 3

Changes in p53, causes a change in morphology and then causes a change in gene expression
- can allow cancerous migration

Question 4

What two forms of cancer does human papillomavirus (HPV) work on?

Answer 4

Skin

Cervical

Question 5

How does HPV cause cancer?

Answer 5

They are able to control cell programming - when the virus is removed the cells change morphology

Question 6

What protein is removed during HPV induced cell programming?

Answer 6

E6 protein

Question 7

What is the cytoskeleton made up of?

Answer 7

• Microtubule
• Intermediate
• Filament
• Microfilament

Question 8

What is a histone?

Answer 8

The beads which are surrounded by DNA

Question 9

What is a nucleosome?

Answer 9

The histone + the DNA surrounding it

Question 10

What is a chromosome?

Answer 10

The highest compaction of DNA

Question 11

What is euchromatin?

Answer 11

open

means that DNA can be transcribed and expressed (active DNA)

Question 12

What is heterochromatin?

Answer 12

Closed (inactive form)

Question 13

What are chromatin fibers?

Answer 13

The DNA which surrounds the histone

Question 14

How many histones make up a nucleosome?

Answer 14

8

Question 15

What are the 8 histones?

Answer 15

A dimer of H3 and H4
A dimer of H2A and H2B
- these join to form a tetramer
- 2 tetramers make an octamer

Question 16

What is the function of H1?

Answer 16

It compacts the DNA around it even more

Question 17

what is a chromatosome?

Answer 17

A nucleosome + a H1 histone

Question 18

What causes a chromatid formation?

Answer 18

Tight coiling of the fiber

Question 19

What happens after tight coiling?

Answer 19

Nucleosomes fold to decrease the length of the fiber
Loops form
These are then compressed

Question 20

What allows the tightening of chromatin fibres around a histone?

Answer 20

The +ve amino acids in the histones and negative DNA

Question 21

What are chromosome territories?

Answer 21

The organisation of the chromosomes in the nucleus

Question 22

What is linker DNA?

Answer 22

The DNA which connects two nucleosomes

Question 23

What does H1 histones cause?

Answer 23

Further compaction and stabilisation

Question 24

What effect does H1 histones have on DNA transcription?

Answer 24

DNA cannot be transcribed

Question 25

Solenoids?

Answer 25

H1 histones oligomerises causing 6 nucleosomes to coil together

Question 26

What happens to solenoids?

Answer 26

They stack on top of each other

Question 27

How do chromatin fibers form loops?

Answer 27

Binding to the nuclear membrane protein

Question 28

What does chromosome territories dependent on?

Answer 28

Gene densities

Question 29

Which chromosome domains are located towards the interior of the nucleus?

Answer 29

The ones which are relatively gene rich

Question 30

How is chromatin regulated?

Answer 30

Post translational modifications

Question 31

What effect does methylation have on histones?

Answer 31

Tighten the interaction between histones and makes it harder to seperate Changes the volume of AA

Question 32

What is the histone code?

Answer 32

The end and the beginning of histones are free from DNA, they are outside

Question 33

What are histone AcetylTransferases (HATs)?

Answer 33

Enzymes which catalyse the transfer of Acetyl group from Acetyl-CoA to the epsilon amino group of lysine present in the N terminus of histones

Question 34

What effect does HATs have on interaction?

Answer 34

Acetylation of lysine = removal of lysine positive charge | Reduction in the interaction between the negative phosphate of DNA and the histone

Question 35

Effect of citrunillation of histone?

Answer 35

regulates interaction with negatively charged DNA = chromatin opening

Question 36

What is citrunillation?

Answer 36

Conversion of arginine to citrulline

Question 37

Effect of histone methylation

Answer 37

Methylation on lysine and arginine Regulates hydrophobic interaction with histones Increases the strength and therefore harder to seperate

Question 38

What controls the binding of H1 histone?

Answer 38

Post translational modifications

Question 39

how are histone modifying enzymes expressed?

Answer 39

In a tissue dependent manner

Question 40

What is the function of histone modifying enzymes?

Answer 40

Cause post translation modifications - therefore responsible for opening and closing the DNA

Question 41

What are the catalytic activities of histone modifying enzymes dependent on?

Answer 41

``` The concentrations of: - Acetyl-CoA - ATP - NADH - FADH - SAM - ketoglutarate - UDP-GlcNAc All produced by TCA cycle ```

Question 42

What can alter transcription levels?

Answer 42

Glucose levels

Question 43

What is the Waddington epigenetic landscape?

Answer 43

Shows how gene programming can determine a cell fate outcome

Question 44

What is the function of p53?

Answer 44

In any form of cellular stress, p53 will accumulate, dimerise, and bind to the DNA and reduce gene expression and therefore trigger repair and apoptosis since the immune cell will identify it as abnormal

Question 45

How does immunotherapy work?

Answer 45

The cancer cells are immune to apoptosis due to the protection from the immune system. Remove the immune system so that it will target the cancer cells

Question 46

What can p53 cause?

Answer 46

``` Cell repair and evolution Senescence Differentiation Cancer cell death Cell migration ```

Question 47

What is senescence?

Answer 47

Loss of ability to divide and grow

Question 48

p53 involvement in enzymes

Answer 48

p53 can regulate expression of most histone modifying enzymes directly -> genome programming p53 regulates expression of rate-limiting enzymes of the TCA cycle -> regulate expression of histone modifying enzymes -> genome programming histone modifying enzymes can regulate p53 activity and p53 protein expression