Lecture 7- Epigenetics: link between genes and environment Flashcards

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1
Q

What are the genes and epigenetics in the music analogy?

A
  • Genes = instruments

- Musicians = epigenetics

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2
Q

What makes identical twins different?

A
  • Identical DNA, different personalities
  • Difference = epigenetics
  • “above genetics”
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3
Q

What makes cells different?

A
  • Identical DNA, different cell types

- Difference = epigenetics “above genetics”

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4
Q

What do epigenetisc do?

A
  • Epigenetics changes the activity of genes in response to environment
  • e.g. Queen Bee= so different eventough only difference is the royal jelly bath during development
  • e.g. plants= flower better if cold winter= people also different depending on when born (weather, season)
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5
Q

What is epigenetics?

A
  • Epigenetic ‘marks’ can act as:
  • A volume control for genes
  • A way to organise our the 2 metres of DNA in every cell.
  • A way to develop different cells with the same DNA
  • A way for you to adapt to your environment
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6
Q

What is an epigenetic mark?

A
  • A small molecule:
  • Methyl
  • Acetyl (COCH3)
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7
Q

Where do the marks go?

A

• Onto DNA (CpG methylation)
• Onto the proteins that package DNA
(histones)
-DNA methylation can go onto DNA, associated with reduction in gene activation, methyl group onto histone tails (that is how they can attach)

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8
Q

How do the marks get there?

A
  • Sequence-specific recruiting factors • Protein transcription factors
  • Non-coding RNA
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9
Q

What is the epigenetic code?

A

-the four ‘R’s: Recruiters, wRiters, Readers and eRasers
1• Sequence-specific factors (recruiters) bind to DNA(= • Transcription factors (proteins)
• Non-coding RNAs)
2.• Epigenetic modifiers (writers) recruited 3. Epigenetic marks (re-)written
4.Epigenetic marks bound (“read”) by complexes of proteins.
5.• Epigenetic marks erased

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10
Q

How does chromatin control gene activity?

A

1.• Loose chromatin structure • Less DNA methylation
• “Active” histone marks
• Genes turned up

2.• Tight chromatin structure • More DNA methylation
• “inactive” histone marks
• Genes turned down

  • it is a reversible process= the epigenetic process(previous slide)
  • combination of loss of methylation = more active gene expression
  • combination of a specific mark and physical structure (active marks= cause chromatin to be loose, inactive marks= tight)
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11
Q

What is the importance of histones in the genetic code?

A

histone (protein) wrapped by DNA, chemcial tags and tail
= epigenome
=shapes teh physical structure of the genome
-if tight= not read, not atcive gene
-loose= active
-epigenetic is flexible

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12
Q

What is the lick a rat study?

A

compare rats= licked and groomed offspring and the ones neglected= grew to be nervous

  • stress pathway affected, a GR gene (glucocorticoid gene)
  • there is evidence that a similar thing happens in humans= when abused as children
  • also PTSD
  • also those in womb
  • when smoking= babies have less methylation
  • plastic after birth and in the womb, we never lose the sensitivity completely
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13
Q

Can epigenetics be reversed?

A
  • yes, by diet or drugs
  • can still be affected by the environment= can reverse the effect of an early environment, possibly
  • yoga, mindfulness, meditation= change genes too!
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14
Q

What in our environment can change epigenetics?

A
1.The good
• B group vitamins
• Soy
• Broccoli
• Tea
• “Good” bugs

2.The bad
• Stress
• Fungicides & pesticides • Fire retardants
• Plasticisers (BPA) • “bad” bugs

  • broccoli= contains many epigenetic molecules, the same case with most vegetables and fruit
  • about 1.5 kg= of bacteria in our body, we feed them through breast milk= short chain oligosaccharides for the bacteria
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15
Q

How did the mice fathers influence the offspring?

A
  1. Male rats fed a high fat diet fathered obese sons.
  2. Male mice fed a low protein diet had offspring with lower levels of cholesterol.
  3. Male pigs fed an “epigenetic diet” had leaner grandchildren.
  4. All were accompanies by epigenetic changes
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16
Q

What are the trans-generational effects of fungicides & pesticides on rats?

A
  • Exposed pregnant rats → several generations of rats with decreased male fertility.
  • These changes linked with a change to DNA methylation
17
Q

What is the evidence of trans-generational effects in humans?

A

-dutch famine in WWII= • Increased risk of heart disease, diabetes, cancer & mental illness as adults
• “Epigenetic legacy” found 60 years later
• Season of conception in The Gambiai nfluences DNA methylation of several genes in the offspring (Waterland et al 2010)
• Maternal carbohydrate intake influences methylation of several genes in the offspring and is linked with obesity (Godfrey et al, 2011)

18
Q

What is the situation with epigenetics and human disease?

A
  • Currently, a small number of diseases shown to have an epigenetic component
  • Cancer
  • some rare syndromes e.g. fragile X syndrome, Rett syndrome
  • “Imprinting” syndromes
  • The future: complex, “multifactorial” diseases e.g.
  • Schizophrenia, depression, anorexia
  • Asthma, allergy
  • Heart disease, obesity, diabetes
  • Epigenetic marks at time 1 that predict health outcomes at time 2
  • Cancer outcomes (Chan et al, 2012)
  • Onset of cardiovascular disease symptoms (Kim et al, 2010)
  • Response to weight loss programs (Cordero et al, 2011; Milagro et al 2011)
  • Childhood obesity (Godfrey et al, 2011)
  • Can we predict future disease risk at birth?