G7

Question 1

how many histone modicfications are possible and why?

Answer 1

280 billion possible modification

each combination of ptm on any number of AA’s of tail could cause a specific phenotype

Question 2

where on a histone is usually modified?

Answer 2

the histone tailprotruding from the nucleosome often serves as a template for epigenetic
modifications.

Question 3

what affect could modifications on histones have?

Answer 3

change binding affinities of nucleosome DNA
shift nucleosomes out of the way
change activation of transcription
recruit protein complexes that regulate chromatin state and gene activity

Question 4

what types of modification can lysine residues go through and what enzymes do this

Answer 4

acetylation/deactylation HAT/HDAC
methylation/demethylation HMT/HDM
ubiquination/deubiquination7
ubiquitin ligase/protease

Question 5

what type of modifications can serine/thereonin go through and which enzymes does this?

Answer 5

phosphorylation/dephosphorylation by kinase phosphatase enzyme

Question 6

what type of modications can arginine go through and what enzymes catalyse this?

Answer 6

methylation (mono/di)
demethylation (citrullination)
PRMT/deiminase

Question 7

what is the histone code hypothesis

Answer 7

transcription of genetic info encoded in DNA is in part regulted by chemical modification to hisstone proteins primarily on their unstructured ends.

Question 8

what is HAT enzyme?

Answer 8

histone acetyl transferase

Question 9

what does methylation cause at H3K4

Answer 9

= lysine residue methylation
transcriptional activation
demethylation = silencing

Question 10

what does methyaltion at H3K9 cause?

Answer 10

silent heterochromatin = silencing

Question 11

what does acetylation at H3K14 cause

Answer 11

transcriptional activation

Question 12

what does methylation (mono/ditri) at H3K27 cause

Answer 12

transcriptional memory
mono = activation
di/tri= repression

Question 13

what does methylation at H3K36 cause

Answer 13

transcriptional elongation.

also lysine residue

Question 14

what does methylation at H3K79 and H4K20 cause

Answer 14

signalling G2/M arrest to allow DNA repair.

Question 15

how can histone modifying enzymes act?

Answer 15

intrinsically (on only single nucleosome) or extrinsically - affect nucleosome:nucleosome int4eractions.
can recruit other proteins to DNA via specific domains.

Question 16

what does histone modification participate in the regualtion of?

Answer 16

many process; transcription
dna repar
chromatin assembly
silencing 
heterochromatin formation.

Question 17

how can chromatin enzymes be involved in cancer

Answer 17

mutations in enzymes = rubinstein-Taby syndrome and cancer
mutations in chromatin remodelling enzymes can cause cancer
mutations in epigentic effector proteins = rett syndrome cancer

Question 18

how can the papilloma virus lead to epidermal cacrinomas?

Answer 18

because contains genes that interact with methylation enzymes and histone modifcation enzymes

Question 19

what can diregualtion of gene expression in cancer cells lead to

Answer 19

- insensitivity to antigrowth signals
evasion of cell death (apoptosis)
immortalisation
impared DNA repair capacity
increased genomic instability
tissue invasion and metastasis (spread of cancer to other parts)

Question 20

what is knudsons two hit hypothesis of carcinogenesis?

Answer 20

one hit = epigentic, promoter methylation

subsequent events eliminating seconf copy of the gene such as a mutation

Question 21

what is an example of dergualtion of imprinting leading to cancer

Answer 21

Lol at the IFG2/GH19 locus leads to colon cancer

Question 22

how can age influence DNA methylation levels ?

Answer 22

Age - tendancy to become hypomethylated with age whereas certain CpG islands become hypermetylated

Question 23

how can diet influence dna methylation levels

Answer 23

diet - nutrition supplies methyl groups for DNA and histones - methylation via folate and methionine pathways as mammals cant synthesize these things.

Question 24

how can the environment influence DNA methylation levels

Answer 24

agents such as arsenic and cadmimum
arsenic - causes hypomethylation of ras gene
cadmium - induce global hypomethylation by inactivation DNMT1. associated with cancers

Question 25

Describe the process by which RB tumour repressor works

Answer 25

H3K9 methylation at promoters in early G1 phase. RB recruits deacetylases and methylases to repress the cyclin E gene
deacetylation and K9 trimethylation of histones results in condensed and transcriptionally repressed chromatin
loss of RB leads to depression of S phase inducing genes and proliferation

Question 26

what are chromatin remodellers?

Answer 26

large mulitsubunit complexes containing an enzymatic ATPase, core subinits and accessory subunits which load/slide or eject nucleosomes and are involved in cancers

Question 27

how are chromatin remodelling complexes affected in cancers

Answer 27

hSWI /SNF subunits are deregulated in cancers

Question 28

what is prader willi syndrome

Answer 28

deregulated genomic imprinting on chromsoome 15
obsessive hunger
mental defects
incomplete sexual development

Question 29

what is angelmans syndrome

Answer 29

loss of paternal genes on chromosome 15 due to imprinting, causes disease by maternal chromosome 15 deletion or inactivation
jerky movemetns
developmenntal dissability

Question 30

what is rubinstein taby syndrome

Answer 30

make half the normal amount of CREB gene invovled in growth
short stature
broad thumbs and toes

Question 31

what is rett syndrome

Answer 31

caused by mutations in x chromosome gene involved in epigenetic regulation
effects nearly always females
small hands and feet and decelerated head growth
jerky movements
mental retardation

Question 32

what is angelamns to prader willi

Answer 32

sister diseases caused by same thing