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L3 Epigenetics > Epigenetic regulation of gene expression > Flashcards

Epigenetic regulation of gene expression Flashcards

1
Q

What are epigenetic traits?

A

Stable, heritable phenotypes resulting from changes to chromatin structure without alterations to DNA sequences

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2
Q

What is chromatin?

A

DNA plus DNA binding proteins (histones)

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3
Q

Which enzymes regulate DNA methylation? (2)

A
  • DNA methyltransferases (DNMTs)
  • Demethylases
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4
Q

What are the functions of epigenetic mechanisms? (2)

A
  • Shape accessibility of genes to transcription machinery
  • Regulate levels of gene expression and sensitivity to extrinsic transcription factors
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5
Q

What is an example of transcription factor recruitment to promoters/enhancers? (3)

A
  • Ecdysone hormone binds to its receptor
  • Hormone-receptor complex enters the nucleus and binds to promoter/enhancer sequences
  • Recruits transcription factors and RNA polymerase to cause transcription
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6
Q

What are the 2 types of methylation?

A
  • DNA methylation (cytosine)
  • Histone methylation (lysine K)
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7
Q

Explain DNA methylation (3)

A
  • Cytosine can be methylated by DNMTs forming 5-methylcytosine/demethylated by demethylases
  • Methylation prevents recruitment of transcription factors and silences genes
  • Methyl groups sit in the major groove so are available for interaction with enzymes and methyl-CpG binding proteins
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8
Q

What sequence is subjected to methylation? (3)

A
  • CpG dinucleotide pair (GC on complementary strand)
  • High densities of CpGs are known as CpG islands and are found in promoter regions
  • Act as regulatory sites for transcription
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9
Q

What is the methylation state of CpG islands in transcriptionally active promoters?

A

Unmethylated

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10
Q

What is the methylation state of CpG islands in transcriptionally silent promoters?

A

Methylated

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11
Q

What is the structure of histones? (2)

A
  • Optomeric
  • DNA is wound around forming nucleosomes
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12
Q

Explain histone modification (2)

A
  • Transcriptionally silent heterochromatin has histones with methylated N-terminal tail
  • Transcriptionally active euchromatin has histones with acetylated N-terminal tail
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13
Q

What is heterochromatin? (2)

A
  • Closed conformation, transcriptionally silent
  • Methylated histones
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14
Q

What is euchromatin? (2)

A
  • Open conformation, transcriptionally active
  • Acetylated histones
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15
Q

What are the 4 core histones?

A
  • Histone H3
  • Histone H4
  • Histone H2A
  • Histone H2B
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16
Q

Which core histone is the most heavily modified?

A

Histone H3

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17
Q

Which enzymes regulate histone acetylation? (2)

A
  • Histone acetyltransferases
  • Histone deacetylases
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18
Q

Which enzymes regulate histone methylation? (2)

A
  • Histone methyltransferases
  • Histone demethylases
19
Q

What are histone kinases?

A

Enzymes that add phosphate groups to serines/threonines of core histones

20
Q

What is the difference between histone methyltransferases and histone acetyltransferases? (2)

A
  • Histone acetyltransferases add acetyl groups to multiple lysines in the N-terminal tail (non-specific)
  • Histone methyltransferases add methyl groups to specific lysines/arginines in the N-terminal tail
21
Q

Which amino acid residue is methylated by histone methyltransferase?

A

Lysine (K) and arginine (R)

22
Q

Which amino acid residue is acetylated by histone acetyltransferase?

23
Q

What are modification ‘readers’?

A

Proteins with modification-specific binding domains

24
Q

Which domain recognises acetylation?

A

Bromo domain

25
Which domain recognises methylated lysines?
Chromo domain
26
What are modification 'erasers'? (2)
- Enzymes with modification-specific catalytic activity - HDACs and HDMs/KDMs
27
What are HDACs?
Histone deacetylases
28
What are HDMs/KDMs?
Histone (Lysine - K) demethylases
29
What are the 2 types of non-coding RNAs?
- Long non-coding RNAs - Short non-coding RNAs
30
What is the function of lncRNAs? (2)
- Form stem loop structures which bind chromatin-associated proteins with transcription regulatory functions - Can shut down/stimulate expression
31
What is an example of lncRNA? (2)
- X chromosome-derived ncRNA Xist - Causes X chromosome inactivation
32
What is the function of short non-coding RNAs? (2)
- miRNAs are transcribed in the nucleus and exported to the cytoplasm where they act as antisense inhibitors of particular mRNAs to prevent expression - piRNAs form complexes which suppress transposable element expression in the nucleus by promoting formation of heterochromatin (silent)
33
What is phenotypic robustness and plasticity? (2)
- Epigenetic mechanisms produce phenotypic robustness during development by regulating expression in a predictable schedule - Also flexible and sensitive to intrinsic/extrinsic physiological signals
34
What are the consequences of phenotypic plasticity? (2)
- Allows beneficial adaptations to improve fitness - Creates capacity for emergence of maladaptive chronic disease states
35
What are the 2 types of phenotypic plasticity?
- Reaction norm - Polyphenism
36
What is reaction norm plasticity?
Phenotypic characteristics change continuously in response to changes in the environment (graded response)
37
What is an example of reaction norm plasticity? (2)
- Muscle mass and physiological function responses to resistance training are proportional to environmental stimulus - Resistance training increases PGC1alpha expression which causes muscle hypertrophy
38
How is PGC1alpha affected by training? (3)
- PGC1alpha is a transcription factor that can be expressed from 2 alternative promoters - 1 promoter is resistance training activated, expression of PGC1alpha4 isoform which causes muscle hypertrophy, contains an extra exon - Other promoter is endurance training activated, expression of PGC1alpha1 and causes muscle adaptation for endurance
39
What molecular processes underpin reaction norm plasticity? (2)
- Set of genes whose expression increases and decreases during muscle loading and unloading, may be positively regulated by PGC1alpha - Accompanied by complementary CpG DNA demethylation and methylation
40
What is polyphenism plasticity?
Discrete transformation of phenotypic characteristics from one type to another when environmental stimulus crosses a threshold quantity
41
What is an example of polyphenism plasticity? (3)
- Predator-induced (secreted molecules) body shape change in Daphnia - Population density-dependent colour change in locusts - Spadefoot toad formation of keratinized mouthparts/convert from ominovore to carnivore in fast-drying pools to accelerate metamorphosis
42
Which human behaviours modulate epigenetic mechanisms and promote chronic disease? (3)
- Exercise - Consumption patterns - Sedentary lifestyle
43
What were the impacts of the Dutch famine 1944-1945? (4)
- Children conceived/first trimester during the famine were born with low birth weight and had a 3x greater risk of coronary heart disease as adults - More advanced pregnancies/conceived after the famine babies were unaffected - First trimester-specific DNA methylation differences present as adults - Development of the thrifty phenotype hypothesis
44
What is the thrifty phenotype hypothesis? (3)
- First trimester is a critical time for defining physiological set points - If resources are scarce the set points are adjusted to maximise use of available resources in the present and the future (permanent switches) - Chronic disease can be a late life manifestation of early life experiences which caused maladaptive plasticity

L3 Epigenetics (15 decks)

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