Epigenetic p53 Flashcards

1
Q

What is epigenetic?

A

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

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2
Q

What do human cancer cells undergo to differentiate?

A

Genome remodeling and genome reprogramming

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3
Q

What happens in regards to p53 in cancer?

A

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

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4
Q

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

A

Skin

Cervical

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5
Q

How does HPV cause cancer?

A

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

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6
Q

What protein is removed during HPV induced cell programming?

A

E6 protein

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7
Q

What is the cytoskeleton made up of?

A
  • Microtubule
  • Intermediate
  • Filament
  • Microfilament
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8
Q

What is a histone?

A

The beads which are surrounded by DNA

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9
Q

What is a nucleosome?

A

The histone + the DNA surrounding it

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10
Q

What is a chromosome?

A

The highest compaction of DNA

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11
Q

What is euchromatin?

A

open

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

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12
Q

What is heterochromatin?

A

Closed (inactive form)

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13
Q

What are chromatin fibers?

A

The DNA which surrounds the histone

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14
Q

How many histones make up a nucleosome?

A

8

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15
Q

What are the 8 histones?

A

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

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16
Q

What is the function of H1?

A

It compacts the DNA around it even more

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17
Q

what is a chromatosome?

A

A nucleosome + a H1 histone

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18
Q

What causes a chromatid formation?

A

Tight coiling of the fiber

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19
Q

What happens after tight coiling?

A

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

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20
Q

What allows the tightening of chromatin fibres around a histone?

A

The +ve amino acids in the histones and negative DNA

21
Q

What are chromosome territories?

A

The organisation of the chromosomes in the nucleus

22
Q

What is linker DNA?

A

The DNA which connects two nucleosomes

23
Q

What does H1 histones cause?

A

Further compaction and stabilisation

24
Q

What effect does H1 histones have on DNA transcription?

A

DNA cannot be transcribed

25
Q

Solenoids?

A

H1 histones oligomerises causing 6 nucleosomes to coil together

26
Q

What happens to solenoids?

A

They stack on top of each other

27
Q

How do chromatin fibers form loops?

A

Binding to the nuclear membrane protein

28
Q

What does chromosome territories dependent on?

A

Gene densities

29
Q

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

A

The ones which are relatively gene rich

30
Q

How is chromatin regulated?

A

Post translational modifications

31
Q

What effect does methylation have on histones?

A

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

32
Q

What is the histone code?

A

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

33
Q

What are histone AcetylTransferases (HATs)?

A

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

34
Q

What effect does HATs have on interaction?

A

Acetylation of lysine = removal of lysine positive charge

Reduction in the interaction between the negative phosphate of DNA and the histone

35
Q

Effect of citrunillation of histone?

A

regulates interaction with negatively charged DNA = chromatin opening

36
Q

What is citrunillation?

A

Conversion of arginine to citrulline

37
Q

Effect of histone methylation

A

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

38
Q

What controls the binding of H1 histone?

A

Post translational modifications

39
Q

how are histone modifying enzymes expressed?

A

In a tissue dependent manner

40
Q

What is the function of histone modifying enzymes?

A

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

41
Q

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

A
The concentrations of:
- Acetyl-CoA 
- ATP 
- NADH 
- FADH 
- SAM 
- ketoglutarate
- UDP-GlcNAc 
All produced by TCA cycle
42
Q

What can alter transcription levels?

A

Glucose levels

43
Q

What is the Waddington epigenetic landscape?

A

Shows how gene programming can determine a cell fate outcome

44
Q

What is the function of p53?

A

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

45
Q

How does immunotherapy work?

A

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

46
Q

What can p53 cause?

A
Cell repair and evolution 
Senescence 
Differentiation 
Cancer cell death 
Cell migration
47
Q

What is senescence?

A

Loss of ability to divide and grow

48
Q

p53 involvement in enzymes

A

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