Epigenetic p53 Flashcards
What is epigenetic?
The study of changes in an organism which causes changes in gene expression but no changes in the genetic code
What do human cancer cells undergo to differentiate?
Genome remodeling and genome reprogramming
What happens in regards to p53 in cancer?
Changes in p53, causes a change in morphology and then causes a change in gene expression
- can allow cancerous migration
What two forms of cancer does human papillomavirus (HPV) work on?
Skin
Cervical
How does HPV cause cancer?
They are able to control cell programming - when the virus is removed the cells change morphology
What protein is removed during HPV induced cell programming?
E6 protein
What is the cytoskeleton made up of?
- Microtubule
- Intermediate
- Filament
- Microfilament
What is a histone?
The beads which are surrounded by DNA
What is a nucleosome?
The histone + the DNA surrounding it
What is a chromosome?
The highest compaction of DNA
What is euchromatin?
open
means that DNA can be transcribed and expressed (active DNA)
What is heterochromatin?
Closed (inactive form)
What are chromatin fibers?
The DNA which surrounds the histone
How many histones make up a nucleosome?
8
What are the 8 histones?
A dimer of H3 and H4
A dimer of H2A and H2B
- these join to form a tetramer
- 2 tetramers make an octamer
What is the function of H1?
It compacts the DNA around it even more
what is a chromatosome?
A nucleosome + a H1 histone
What causes a chromatid formation?
Tight coiling of the fiber
What happens after tight coiling?
Nucleosomes fold to decrease the length of the fiber
Loops form
These are then compressed
What allows the tightening of chromatin fibres around a histone?
The +ve amino acids in the histones and negative DNA
What are chromosome territories?
The organisation of the chromosomes in the nucleus
What is linker DNA?
The DNA which connects two nucleosomes
What does H1 histones cause?
Further compaction and stabilisation
What effect does H1 histones have on DNA transcription?
DNA cannot be transcribed
Solenoids?
H1 histones oligomerises causing 6 nucleosomes to coil together
What happens to solenoids?
They stack on top of each other
How do chromatin fibers form loops?
Binding to the nuclear membrane protein
What does chromosome territories dependent on?
Gene densities
Which chromosome domains are located towards the interior of the nucleus?
The ones which are relatively gene rich
How is chromatin regulated?
Post translational modifications
What effect does methylation have on histones?
Tighten the interaction between histones and makes it harder to seperate
Changes the volume of AA
What is the histone code?
The end and the beginning of histones are free from DNA, they are outside
What are histone AcetylTransferases (HATs)?
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
What effect does HATs have on interaction?
Acetylation of lysine = removal of lysine positive charge
Reduction in the interaction between the negative phosphate of DNA and the histone
Effect of citrunillation of histone?
regulates interaction with negatively charged DNA = chromatin opening
What is citrunillation?
Conversion of arginine to citrulline
Effect of histone methylation
Methylation on lysine and arginine
Regulates hydrophobic interaction with histones
Increases the strength and therefore harder to seperate
What controls the binding of H1 histone?
Post translational modifications
how are histone modifying enzymes expressed?
In a tissue dependent manner
What is the function of histone modifying enzymes?
Cause post translation modifications - therefore responsible for opening and closing the DNA
What are the catalytic activities of histone modifying enzymes dependent on?
The concentrations of: - Acetyl-CoA - ATP - NADH - FADH - SAM - ketoglutarate - UDP-GlcNAc All produced by TCA cycle
What can alter transcription levels?
Glucose levels
What is the Waddington epigenetic landscape?
Shows how gene programming can determine a cell fate outcome
What is the function of p53?
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
How does immunotherapy work?
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
What can p53 cause?
Cell repair and evolution Senescence Differentiation Cancer cell death Cell migration
What is senescence?
Loss of ability to divide and grow
p53 involvement in enzymes
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
