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Clinical Nutrition > Epigenetics > Flashcards

Epigenetics Flashcards

1
Q

what is epigenetics?

A

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

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2
Q

what is epigenetics represented by?

A

chromatin modifications

  • DNA methylation
  • histone modification
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3
Q

describe how methylation/acetylation affect histones

A
  • methylation: DNA packed tightly, transcription factors cannot access dna–> GENE NOT EXPRESSED
  • acetylation: loose packing of chromosomes, transcription factors can bind DNA–> GENE EXPRESSED
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4
Q

what is level of methylation if gene inactive?

A

high level of methylation

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5
Q

what is level of methylation if gene active?

A

low levels of methylation

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6
Q

how does methylation occur?

A

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

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7
Q

what is assoc w normal ageing process?

A

de-regulation of epigenetics

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8
Q

what is an exposome?

A

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

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9
Q

what may epigenetics explain?

A

how different phenotypes arise from the same genotype

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10
Q

what is associated with altered human cancer & CVD risk

A

abnormal histone regulation and DNA methylation

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11
Q

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

A
  • curcumin
  • sulforaphene
  • polyphenols
  • folates
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12
Q

specifically what polyphenols?

A

green tea polyphenols, soy and berry isothiocyanates

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13
Q

what are mechanisms of epigenetic gene regulation by histone modification?

A

sulforaphene- HDAC inhibition

curcumin- HAT inhibition

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14
Q

what is sulforaphene

A

sulphur containing compound present in cruciferous veg

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15
Q

what is curcumin

A

major component of turmeric & has anti-inflammatory properties

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16
Q

what does HAT inhibition cause

A

increases apoptosis, inhibits proliferation & reduces inflammation

17
Q

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

A

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)
18
Q

what is DNMT responsible for?

A

catalyse transfer of methyl group to DNA

19
Q

ways to measure GLOBAL DNA methylation?

A
  • methyl donor acceptor assay
  • liquid chromatography
  • ELISA
20
Q

what is the gold standard to measure global dna methylation?

A

liquid chromatography

21
Q

how does liquid chromatography work?

A

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

22
Q

how to measure GENE-SPECIFIC DNA methylation?

A

pyrosequencing

23
Q

how does pyrosequencing work?

A

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

24
Q

effect of folates on methylation?

A

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

25
Q

relationship between dietary folates and cancer?

A

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

26
Q

relationship between folates and CVD?

A

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

27
Q

why do low folate levels= hyperhomocysteinaemia?

A

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

28
Q

what are polyphenols and where are they found?

A

anti-oxidants

fruit, veg, cereals, herbs, spices, EVO, soy, legumes, chocolate, tea, coffee, wine and beer

29
Q

which polyphenols are assoc w reduced risk of prostate cancer?

A

isoflavone and soy

30
Q

what substance is inversely assoc w rectal cancer?

A

catechin from green tea

31
Q

what is green tea associated with?

A

reduced lung cancer in smokers and breast cancer

32
Q

how do polyphenols modify methylation and carcinogenesis?

A

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

33
Q

what is atherosclerosis characterised by?

A
  • 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
34
Q

what is DNA like in atherosclerotic plaques?

A

hypomethylated

35
Q

what does the gut microbiome convert?

A
  • glucosinolates to isothiocyanates (ITCs)

- fibre to SCFA

36
Q

where are glucosinolates found?

A

cruciferous veg

37
Q

what are ITCs?

A

strong anti-cancer compounds

38
Q

what is butyrate?

A

potent modulator of apoptosis

Clinical Nutrition (5 decks)

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