M1-Lecture 2 Flashcards

1
Q

What leaves a chemical “signature” on the genes that determines whether & how the genes are expressed.

A

Experiences

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2
Q

Different genotypes respond to environmental stimulus differently? T/F

A

TRUE

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3
Q

The three components that make up a phenotype:

A

Epigenetics, Environment, and Genetics.

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4
Q

Give example of SNPs:

A

SNP mutation resulting in gene variants that can influence sensitivity to one’s environment.

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5
Q

Example of Epigenetics:

A

microRNA and ncRNA

CpG methylation

Histone modification

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6
Q

Example of environment:

A

Nutrition, toxins, drugs, pathogens

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7
Q

Embryonic stem cell divisions:

A

Mesoderm: middle layer

Endoderm: Internal layer

Ectoderm: External layer

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8
Q

How did the cells in our body become different & why do they stay like that?

A

Once specialized, the changes are permanent.

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9
Q

DNA not always in chromosome form but open? T/F

A

TRUE

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10
Q

Modifying the histone will expose the DNA? T/F

A

TRUE

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11
Q

What are the factors that affect epigenetic mechanisms:

A

Development (utero, childhood)

Environmental chemicals

Drugs/pharmaceuticals

Aging

Diet

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12
Q

Mention a few epigenetic modifications:

A

DNA methylation

Histone modification

Chromatic accessibility

Non-coding RNA regulation

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13
Q

What is an epigenetic factor found in some dietary sources:

A

Methyl group

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14
Q

DNA methylation function:

A

Can tag DNA and activate or repress genes.

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15
Q

Blank are proteins around which DNA can wind for compaction and gene regulation.

A

Histones

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16
Q

What alters the extent to which DNA is wrapped around histones & availability of genes in DNA to be activated?

A

Epigenetic factors (which can give rise to health endpoints).

For instance, increased histone acetylation generally leads to a more open chromatin structure, facilitating gene expression, while DNA methylation typically silences genes by promoting a closed chromatin configuration.

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17
Q

Biological dogma states that genetics regulates all inherited traits across generations, & epigenetic modifications are reset upon passage of germ line? T/F

A

TRUE

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18
Q

What is responsible for the functional use & stability of the genetic info our chromosomes hold & connects genotype to phenotype.

A

Epigenome

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19
Q

Epigenetic inheritance occurs through meiosis and several generations, including trans-generational? T/F

A

TRUE

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20
Q

The nucleosomes of DNA and histones are organized into what:

A

Chromatin

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21
Q

Change to the structure of chromatin influences gene expression: T/F

A

TRUE

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22
Q

Epigenetic modifications - when is a gene “switched on”:

A

Active “open” chromatin
Unmethylated cytosines [bases in DNA] (white circles)
Acetylated histones (adding acetyl group to lysine residues on histone proteins) reduces + charge on histones for relaxed and open chromatin structure for gene transcription.

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23
Q

Epigenetic modifications: when is a gene “switched off”

A

Silent (condensed) chromatin
Methylated cytosines (red circles)
Deacetylated histones

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24
Q

Types of histone modifications:

A

Acetylation
Methylation
Sumoylation
Phosphorylation
Ubiquitination

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25
Q

Define the types of histone modification:

A

Acetylation: adding acetyl group to lysine (found in histone tails) residues on histones (makes chromatin open)

Methylation: addition of methyl groups to lysine/arginine (found in the tails of histone) residues on H (activate/repress gene expression) Note: depends number of methyl added & specific residues affected.

Phosphorylation: adding phosphate group to serine, threonine, or tyrosine residues on H, affecting chromatin structure, gene e. common in cell divi. & DNA damage repair.

Ubiquitination: addition to H. influence chromatin s. & gene expression, histone degradation or altering chromatin dynamics.

Sumoylation: addition of SUMO to H, impact chromatin structure & gene expression, gene silencing.

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26
Q

In condensed nucleosomes, histones are methylated and unacetylated. T/F

A

TRUE

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27
Q

Uncondensed nucleosomes, histones are unmethylated & acetylated. T/F

A

TRUE

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28
Q

Active vs. inactive regions of chromatin:

A

Active chromatin: unmethylated DNA & acetylated histones.

Inactive chromatin:
Methylated DNA & deacetylaed histones

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29
Q

An epigenetic tag (methylated vs. unmethylated) is placed on targeted DNA, marking it with a special status that activated or silences genes? T/F

A

TRUE

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30
Q

DNA methylation or unmethylation are reversible modifications and benefit?

A

Specific genes can be expressed or silenced genes based on deve. or biochemical cues, such as changes in hormone levels, dietary components or drug exposures.

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31
Q

What does histone code hypothesis state:

A

Activity of chromatin region depends on degree of chemical modification of histone tailes.

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32
Q

What enzymes place acetyl groups on histone?

A

Acetyltransferases

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33
Q

What enzyme removes acetyl groups from histones?

A

histone deacetylases

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34
Q

Methyl groups are placed on DNA by what?

A

DNA methyl transferases

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35
Q

Demethylation of DNA can either be passive (through replication process) or active or both? T/F

A

TRUE

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36
Q

Methylated promoters & enhancers keep genes inactive? T/F

A

TRUE

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37
Q

What proves epigenetic inheritance?

A

Enzymes methylate DNA in the same spot on new cells.

38
Q

70-90% of all CpG dinucleotides exist in methylated form? T/F

A

TRUE

39
Q

CpG islands demonstrated methylation variability. T/F

A

TRUE

40
Q

DNA methylation occurs often at CpG sites. T/F

A

TRUE

41
Q

These sites are embedded in in genome in discrete (terminal CpG islands) 0.5-0.2 kb, in the adjacent regions of transcriptional start sites.

A

CpG sites

42
Q

More than half the genes in the genome contain CpG islands within their promoter & are usually unmethylated in normal cells (house-keeping genes, which are always on). T/F

A

TRUE

43
Q

Methylation marks occur throughout embryological deve.? T/F

A

TRUE

44
Q

Methylation of promoters & enhancers prevent RNA polymerase from binding to the promoter and blocks gene activity? T/F

A

TRUE

45
Q

DNA methylation is a component of one-carbon metabolism pathway and depends on enzymes & dietary micronutrients cofactors, including folate, choline and betaine. T/F

A

TRUE

46
Q

See diagram on

A

One Carbon Metabolism Pathway

47
Q

Genes can have multiple tissue specific enhancers? T/F

A

TRUE

48
Q

DNA methylation -
Blank maintains DNA methylation pattern through cell devisions in proliferating cells.

A

DNMT1

49
Q

DNA methylation -

Blank is responsible for establishing new DNA methylation patterns during development?

A

DNMT3a/b

50
Q

Examples of cells in our body that divide rapidly?

A

Hair follicle cells, GI tract (vomiting), and RBC and WBC.

51
Q

Sequence-specific molecules that guide protein complexes to specific sites in the chromatin for transcriptional repression.

A

Long non-coding RNA (IncRNA)

52
Q

IncRNA has important role in X-chromosome inactivation, imprinting. T/F

A

TRUE

53
Q

What are small RNA molecules (22 nucleotides)?

A

miRNA

54
Q

miRNA are post-transcriptional regulators of gene expression? T/F

A

TRUE

55
Q

How do miRNA regulate gene expression?

A

By binding to mRNAs and promoting their degradation or inhibiting their translation

56
Q

Examples of Non-coding RNAs:

A

miRNA and circRNAs

57
Q

What are covalently closed & circular-shaped subgroup of ncRNAs?

A

circRNAs

58
Q

circRNAs are known as the major epigenetic regulators of pathogenesis? T/F

A

TRUE

59
Q

How do circRNAs regulate gene expression?

A

By sponging microRNAs, binding to proteins or they can be translated into proteins themselves.

60
Q

Blank is central mechanism driving normal development & programming.

A

Epigentics

61
Q

List and explain epigenetic mechanisms:

A
  1. Histone modification:
    Either acetylation or methylation. Affect how tightly DNA is wrapped around histones & regulate gene expression.
  2. DNA methylation:
    adding methyl groups to DNA, cytosine bases, silencing genes by preventing transcription machinery from accessing DNA.
  3. Non-coding RNAs: RNA molecules that do not code for proteins, like microRNAs & Long non-coding RNAs. Regulate gene expression by interacting with mRNA & chromatin.
62
Q

Blank refers to erasure & remodelling of epigenetic marks.

A

Epigenetic reprogramming

63
Q

Developmental stages in which epigenome undergoes profound programming?

A
  1. Pre-implantation
    - De-methylation
    - X-chromosome inactivation
    - Tissue-specific methylation (morphogenesis)
  2. Gametogenesis
    - De-methylation
    - X-chromosome activation
    - Imprinting
64
Q

Diet-induced phenotypic change:

Blank refers to changes in maternal diet can produce changes in DNA methylation that can affect the phenotype of the offspring.

A

Agouti gene

65
Q

Although agouti gene is dominant, mothers fed (folate, choline, & betaine) - donate methyl group} did not produce young expressing the phenotype. T/F

A

TRUE

66
Q

In pregnant rats, a low protein diet predisposes the pups to diabetes, hypertension, & obesity. T/F

A

TRUE

67
Q

Rat starved in vetro, express PPARalpha in their liver that leads to greater fat storage. T/F

A

TRUE

68
Q

PPARalpha helps with metabolism and conserve. T/F

A

TRUE

69
Q

Temperature is not the only factor in sex determination. T/F

A

TRUE

70
Q

Injection of estrogen in turtle eggs generates females, regardless of temp.? T/F

A

TRUE

71
Q

High levels of aromatase is linked with formation of ovaries. T/F

A

TRUE

72
Q

Aromatase activity or its expression may be temp dependent. T/F

A

TRUE

73
Q

What pathways are activated when honyebees are fed royal jelly (royal actin which binds EGFR)?

A

TOR and MAPK pathways

74
Q

TOR AND MAPK PATHways increase body size & acceletates development, as well as Juvenile hormone (JH) that promotes ovary deve.

A

TRUE

75
Q

Honeybees have methylated DNA like vertebrates - Dnmt3. T/F

A

TRUE

76
Q

Reducing Dnmt3 promotes the frequency of queens? T/F

A

TRUE

77
Q

Characteristics of genes rarely methylated:

A

Less fearful
Modest HPA responses to stress

78
Q

Characteristics of genes highly methylated:

A

Fearful
heightened HPA responses to stress

79
Q

Stress hormones affect DNA methylation? T/F

A

True

80
Q

Tactile stimulus (licking & grooming) regulates synthesis of glucocorticoid receptor in hippocampus? T/F

A

True

81
Q

The binding sites for transcription factor NGF-1 (enhancer for glucocorticoid receptor gene) is methylated 1 day but is lost if licked & groomed. What does this mean?

A

Rats that receive lots of licking & grooming, have more GR in the brain & are able to deal with stress.

82
Q

Maternal behavior of low grooming is carried to the next generation. T/F

A

True

83
Q

Intergenerational Effects:

A

Maternal environmental exposures (F0) have direct effects on germ cells/developing fetus (including germ line of fetus, altering phenotype [F1] and possibly grandchild [F2], or

the paternal line, father’s exposure has direct effects on germ cells that form the child.

84
Q

Trangenerational effects:

A

Epigenetic information is transmitted across generation, but can only be proved if effect is transmitted to F2 (for maternal & paternal line in which exposure occured only before conception.

or F3 (on maternal line when exposure occurs during pregnancy) or future generations.

85
Q

Epigenetic leads to structural changes during the period of gestation? T/F and give example.

A

True

Example: Epigenetics can result in altered organ structure leading to Brain sparing - so most of our oxygen & nutrient delivery goes toward the brain (based on the size of the arrow)

Also, this may lead to fetal hypoxia and placental dysfunction.

86
Q

Besides structural changes, epigenetics also consists of cellular aging, altered homeostatic endpoints? T/F

A

True

87
Q

Homeostasis does not involve keeping conditions static, it involves keeping conditions within tightly regulated physiological tolerance limits? T/F

A

True

88
Q

Earlier intervention improves functional capacity & responses to new challenges? T/F

A

True

89
Q

What does intervention look like in the context of DOHaD?

A

Education

Pre-conception, Pre-natal and Post-natal support

Investment in children and families

90
Q
A