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HSS4102 > Module 1 > Flashcards

Module 1 Flashcards

1
Q

What is epigenetics?

A

study of changes in organisms caused by modifications of GENE EXPRESSION

NOT due to an alternation in the genetic code itself

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2
Q

What is an epigenetic modification?

A

when there is a change that encodes genes in brain cells

temporary or permanent

positive or negative influences

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3
Q

What is the epigenome responsible for?

A

functional use and stability of info
connects genotype to phenotype

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4
Q

What are the 3 different modifications which DNA undergo to change gene expression (epigenetic modification)?

A
  1. Histone modification
  2. DNA methylation
  3. Non-coding RNAs
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5
Q

Chromatin is condensed which means the gene is inactivated or activated?

A

inactivated (switched off) and silent

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6
Q

Chromatin is open which means the gene is inactivated or activated?

A

activated (turned on) and expressed

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7
Q

What do active regions of chromatin contain?

A

lots of unmethylated DNA

high levels of acetylated histones

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8
Q

What do inactive regions of chromatin contain?

A

lots of methylated DNA

high levels of deacetylated histones

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9
Q

What is placed on targeted DNA to mark it to either turn DNA on or off?

A

epigenetic tag

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10
Q

What are 5 histone modifications that can occur?

A
  1. acetylation ***
  2. methylation ***
  3. sumoylation
  4. Phosphorylation
  5. Ubiquitination
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11
Q

What is the “histone code hypothesis”?

A

activity of a chromatin region depends on the degree of chemical modification of histone tails

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12
Q

What enzyme places acetyl groups on histones?

A

histone acetyltransferases

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13
Q

What enzyme removes acetyl groups on histones?

A

histone deacetylases

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14
Q

What enzyme places methyl groups on DNA?

A

DNA methyl transferases (DNMTs)

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15
Q

Can Demethylation of DNA be passive or active?

A

either!
or combo!

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16
Q

Where does DNA methylation occur on DNA?

A

CpG sites

-located adjacent regions of transcriptional startsites

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17
Q

When the promoter and enhancers are methylated on DNA, what happens?

A

prevents RNA Polymerase from binding to promoter

BLOCKS GENE ACTIVITY

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18
Q

DNA methylation is apart of what pathway and is dependent on what 2 things?

A
  • one carbon metabolism pathway
    1. several enzymes
    1. dietary micronutrient cofactors (folate, choline, betaine)
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18
Q

What does DNMT1 do in DNA methylation process?

A

maintains the DNA methylation pattern

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19
Q

What does DNMT3a/b do in the DNA methylation process?

A

responsible for establishing NEW DNA methylation patterns during development

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20
Q

What are the 3 non-coding RNAs important in epigenetics?

A
  1. long non-coding RNA (lncRNA)
  2. miRNA
    3.circRNAs
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21
Q

What is lncRNA known to do?

A

X-chromosome inactivation

imprinting (gene is silenced, and gene from other parent is expressed)

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22
Q

What is miRNA known to do?

A

post transcriptional regulators of gene expression

creates a feedback loop that can repress key enzymes that drive epigenetic remodeling

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23
Q

What are circRNAs known for?

A

MAJOR EPIGENETIC REGULATORS!!!

closed and circular shaped

regulate gene expression by sponging microRNAs, binding proteins or translating them into proteins themselves

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24
Q

Is epigenetics a central mechanisn driving normal development and programming?

A

YES!

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25
Q

What is the “Agouti gene experiment” in epigentics?

A

showed how changes in maternal diet can produce changes in DNA methyaltion —> affecting phenotype of offspring

has to do with colour of fur (more methylation of agouti gene = more brown, less methylation of agouti gene= more yellow)

Pregnant rats fed low protein diet —> predisposed her pups to diabetes, hypertension, obesity

Rats starved in utero –> showed greater fat storage (expressed for PPAR - alpha in their liver)

26
Q

What is epigenetic reprogramming?

A

getting rid of and remodeling of epigenetic marks

27
Q

What are the 2 crucial developmental stages where the epigenome undergoes profound reprogramming?

A
  1. Pre-implantation
  2. gametogenesis
28
Q

What is the “mouse licking and grooming experiment 1” showing?

A
  • how neonatal care affects epigenetics and adult behaviour

-2 mothers
mother A –> attentive to pups (licking and grooming lots)
Mother B –> inattentive to pups (no licking or grooming)

  • brains of growing pups
    Mother A pups –> very little methylation of genes, LOW stress and less fearful
    Mother B pups –> lots methylation of genes, HIGH STRESS and fearful
29
Q

What is the “mouse licking and grooming experiment 2” showing?

A

pups got switched at birth (inattentive mother pups with attentive mother, attentive mother pups with inattentive mother)

results:
- inattentive pups LOW stress
- attentive pups HIGH stress

30
Q

Overall what does the mouse licking experiment show?

A
  • it was not the pups genes that increased their chance of being more stressed
  • it was their ENVIRONMENT

-methylation affected by stress

  • Rats that received lots of grooming have more of the stress hormone (glucocorticoid hormone) in the brain, therefore able to deal with stress
31
Q

What is the difference between integenerational and transgenerational epigenetic inheritance?

A

intergenerational = when maternal or paternal environment exposures have DIRECT effect on germs cells or developing fetus

transgenerational = where epigenetic information is transmitted across generations, ONLY if the effect of exposure is transmitted to grandchild (from paternal line or in maternal line before conception) or grandchild from maternal exposure during pregnancy
*ACROSS FUTURE GENERATIONS!

32
Q

What are the 3 other mechanisms of DoHAD besides epigenetics?

A
  1. structural changes (brain sparing)
  2. cellular aging (telem
  3. altered homeostatic setpoints
33
Q

What is brain sparing?

A

adaptive response where the brain obtains the necessary resources for its proper development and functioning

circulates to preserve oxygen and nutrient supply to brain in order to function

caused by lack of oxygen and nutrient delivery

34
Q

What is cellular aging?

A

has to do with “telomere shortening” –> starts to dig into the good stuff of our DNA

early life exposures can cause age related disorders (CVD, metabolic diseases, cancer, cognitive disordes, impaired immune function)

35
Q

What are 3 homeostatic setpoints that can be altered due to early life exposures?

A
  1. stress hyperactivity –> HPA axis
  2. Altered microbiome
  3. altered energy homeostasis –> fat/glucose/insulin metabolism, appetite regulation
36
Q

Is early intervention the key to decrease the potential negative health outcomes in the future?

A

YES!!

37
Q

What are 3 things we can do to intervene the negative programming?

A
  1. educate EVERYONE
  2. pre-conception, pre-natal, and post natal support (nutritious food, lactation specialists, social supports, health care)
  3. investment in children and families (pre-school care, child care, housing , all of this affordable)
38
Q

When are epigenetic tags established?

A

during development of fetus

39
Q

can epigenetic tags be modified throughout life positively or negatively?

A

YES
based on diet and environmental exposures

40
Q

What do epigenetic tags do?

A

control the expression of genes that function in embryonic development

41
Q

What 5 events co-occur with epigenetics?

A
  1. erasure and re-establishment of DNA methylation marks
  2. genetic imprinting
  3. X-chromosome inactivation
  4. development of pluripotent stem cells
  5. differentiation of somatic cells
42
Q

Does each cell have its own epigenetic pattern?

A

YES

43
Q

Following fertilization, what happens to paternal genome?

A

undergoes DNA methylation and histone modifcation instantly

44
Q

Following fertilization, what happens to maternal genome?

A

demethylated gradually
new wave of embyronic methylation is started –> gives blueprint for tissues of devloping embryo

45
Q

what happens once paternal and maternal genomes combine in the same cell?

A

-DNA patterns are almost completely erased

  • some genes remain “imprinted” with methyl marks to see what gene is from what parent –> maintained throughout life of offspring
46
Q

What are imprinted genes?

A

genes whose expression is determined by the parent that contributed them

47
Q

What are nutrigenomics?

A

study of how food and food constituents effect gene expression

48
Q

Does your mothers diet during pregnancy and you diet as an infant affect your epigenome?

A

YES! —> sticks with you into adulthood!

49
Q

Diets with too little methyl-donating folate or choline before or just after birth causes what?

A

regions of genome to be under-methylated for life

decreases DNA methylation

50
Q

Are epigenetic modifications reversible?

A

yes

51
Q

is there an assocationbetween the effects of epigenetics and CVD during aging?

A

yes

52
Q

How does epigenetic modifications play a role in Diabetes (type 2)?

A
  • altered DNA methylation in…
    1. pancreatic islets
    2. adipose tissue
    3. skeletal muscle
    4. liver
53
Q

How does epigenetic modifications play a role in “fragile X syndrome” (Mental health)?

A

abnormality of FMR1 gene

Too many CGGs –> CpG islands at promoter region of FMR1 gene become methylated —> NOT NORMAL —> turns gene OFF

54
Q

How does epigenetic modifications play a role in schizophrenia and other mood disorders?

A

DNA rearrangements in the DNMT genes

DNMT1 is overexpressed in GABA-ergic inteneurons

55
Q

Does stress have an impact on methylation of DNA?

A

yes!

56
Q

How does epigenetic modifications play a role in immunity?

A

loss of control in acceltylation and methylation –> messes up coordination between DNA accessiblity and permit recombination –> affects cells to produce immune response against specific antigen

57
Q

How does epigenetic modifications play a role in “systemic lupus erythematosus”?

A

SLE = develop autoantiboides against nuclear antigens affecting any organ system and tissue

caused by dysregulation of T lymphocytes

58
Q

How does epigenetic modifications play a role in cancer?

A

DNA HYPOmethylation –> activate oncogenes, initiate chromosome instability

DNA HYPERmethylation –> silents tumor suppressor genes

59
Q

As we age, gene promoters become hypermethylated and CpGs of non-coding centrometric repeat regions become HYPOmethylated. True or False

A

TRUE

60
Q

What have we seen in regards to chronic diseases and epigenetic modifcations?

A

-alot to do with DNA methylation

61
Q

What are “Sirtuins”?

A

-regulatory role in metabolism and aging

62
Q

What are 3 things sirtuins do?

A
  1. deacetylate histones and several transcriptional regulators in nucleus/cytoplasm/mitchondria
  2. regulate fat and glucose metabolism based in response to physiological changes in energy levels
  3. anti-aging protein
63
Q
A

HSS4102 (7 decks)

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