Epigenetics

Question 1

what is epigenetics?

Answer 1

processes that regulate changes in gene expression, NOT associated with alterations in coding of DNA sequence (mechanism that described cell phenotype without affecting genotype)

Question 2

what is epigenetics represented by?

Answer 2

chromatin modifications

• DNA methylation
• histone modification

Question 3

describe how methylation/acetylation affect histones

Answer 3

• methylation: DNA packed tightly, transcription factors cannot access dna–> GENE NOT EXPRESSED
• acetylation: loose packing of chromosomes, transcription factors can bind DNA–> GENE EXPRESSED

Question 4

what is level of methylation if gene inactive?

Answer 4

high level of methylation

Question 5

what is level of methylation if gene active?

Answer 5

low levels of methylation

Question 6

how does methylation occur?

Answer 6

SAM (universal methyl donor) donates methyl group to CYTOSINE in DNA

Question 7

what is assoc w normal ageing process?

Answer 7

de-regulation of epigenetics

Question 8

what is an exposome?

Answer 8

everything in environment that individual exposed to ie diet, drugs, chemicals, pollutants etc

Question 9

what may epigenetics explain?

Answer 9

how different phenotypes arise from the same genotype

Question 10

what is associated with altered human cancer & CVD risk

Answer 10

abnormal histone regulation and DNA methylation

Question 11

what are the dietary agents that significantly impact on epigenetic regulation of gene expression?

Answer 11

• curcumin
• sulforaphene
• polyphenols
• folates

Question 12

specifically what polyphenols?

Answer 12

green tea polyphenols, soy and berry isothiocyanates

Question 13

what are mechanisms of epigenetic gene regulation by histone modification?

Answer 13

sulforaphene- HDAC inhibition

curcumin- HAT inhibition

Question 14

what is sulforaphene

Answer 14

sulphur containing compound present in cruciferous veg

Question 15

what is curcumin

Answer 15

major component of turmeric & has anti-inflammatory properties

Question 16

what does HAT inhibition cause

Answer 16

increases apoptosis, inhibits proliferation & reduces inflammation

Question 17

what are mechanisms of epigenetic gene regulation by DNA methylation in cancer?

Answer 17

becomes aberrant in 2 ways:

1. whole genome hypomethylation (increased gene expression- can accelerate carcinogenesis if occurs in proto-oncogenes)
2. CPG islands become hypermethylated (can cause gene silencing if occurs in promotory regions & accelerate carcinogenesis if occurs in tumour suppressor genes)

Question 18

what is DNMT responsible for?

Answer 18

catalyse transfer of methyl group to DNA

Question 19

ways to measure GLOBAL DNA methylation?

Answer 19

• methyl donor acceptor assay
• liquid chromatography
• ELISA

Question 20

what is the gold standard to measure global dna methylation?

Answer 20

liquid chromatography

Question 21

how does liquid chromatography work?

Answer 21

directly measures methylated cytosines in DNA, expresses these as a % of methylated DNA across genome

Question 22

how to measure GENE-SPECIFIC DNA methylation?

Answer 22

pyrosequencing

Question 23

how does pyrosequencing work?

Answer 23

uses gene specific primers to measure methylation in specific gene portions (measures both hypo & hypermethylation in gene regions)

Question 24

effect of folates on methylation?

Answer 24

depletion of folate induces hypomethylation HOWEVER this is not seen in healthy human subjects

Question 25

relationship between dietary folates and cancer?

Answer 25

reduced risk of CRC & polyps in people w highest intakes of folate/blood folate levels

Question 26

relationship between folates and CVD?

Answer 26

low folate status associated with increased risk of vascular disease & hyperhomocysteinaemia (cardiotoxin)

Question 27

why do low folate levels= hyperhomocysteinaemia?

Answer 27

folate and b12 serve as co-factors in converting homocysteine --> methionine therefore in absence /deficiency of these: elevated levels of homocysteine

Question 28

what are polyphenols and where are they found?

Answer 28

anti-oxidants | fruit, veg, cereals, herbs, spices, EVO, soy, legumes, chocolate, tea, coffee, wine and beer

Question 29

which polyphenols are assoc w reduced risk of prostate cancer?

Answer 29

isoflavone and soy

Question 30

what substance is inversely assoc w rectal cancer?

Answer 30

catechin from green tea

Question 31

what is green tea associated with?

Answer 31

reduced lung cancer in smokers and breast cancer

Question 32

how do polyphenols modify methylation and carcinogenesis?

Answer 32

inhibit DNMT activity & reverse DNA hypermethylation. Do this by indirect inhibition or competitive inhibition

Question 33

what is atherosclerosis characterised by?

Answer 33

- Smooth Muscle Cells change from contractile to synthetic phenotype - Over-expression of growth factors & increased SMC proliferation - Migration and invasion of SMC's to luminal intima

Question 34

what is DNA like in atherosclerotic plaques?

Answer 34

hypomethylated

Question 35

what does the gut microbiome convert?

Answer 35

- glucosinolates to isothiocyanates (ITCs) | - fibre to SCFA

Question 36

where are glucosinolates found?

Answer 36

cruciferous veg

Question 37

what are ITCs?

Answer 37

strong anti-cancer compounds

Question 38

what is butyrate?

Answer 38

potent modulator of apoptosis