Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MBG 4110 Final Exam > Metabolism and Epigenetic Transgenerational Epigenetic Inheritance > Flashcards

Metabolism and Epigenetic Transgenerational Epigenetic Inheritance Flashcards

1
Q

What is Acetyl CoA? What does it do? How is it produced?

A

Acetyl CoA is a source of acetyl groups for Histone Acetylation (HATS), so they are a co-factor for HATs
Acetyl CoA acetylates everything
Acetyl CoA is produced by fatty acid oxidation and alcohol metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What happens if you have excess energy?

A

There would more acetyl CoA and as such, histones would be a bit more acetylated than they would be otherwise

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is NAD? How is produced?

A

NAD is a co-factor of Histone Deacetylates (Sir2 homologues)
NAD is produced from tryptophan and Vit B3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How is NAD and acetyl CoA related?

A

A link does exist between Acetyl CoA and NAD pathways
The NAD using SIRT1 activates the AceCS1 enzyme via protein de-acetylation, which in turn produces the metabolite acetyl-CoA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is SAM and SAH? How are they produced?

A

SAM is a donor of methyl groups for DNA-methyl transferases and histone methyl transferases, and once the methyl group is donated, it becomes SAH
SAM and SAH are produced by folic acid and Vitamin B12

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is SAH?

A

SAH acts as an inhibitor of all methyl transferases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is FAD?

A

FAD is a cofactor for histone demethylases, like LSD1 and LSD2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How does Acetyl CoA stimulate HATs? There is a figure to help explain this

A

Acetyl CoA is the donor of acetyl groups for HATs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How does NAD stimulate HDACs? There is a figure to help explain this

A

NAD is the regulatory co-factor of Histone Deacetylases
NAD is produced by NAM
NAM is an inhibitor of histone deacetylation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How does NAD and Acetyl-CoA work together?

A

There is a diagram to help explain this

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How does SAM and SAH stimulate HMT and DNMT and repress them?

A

SAM is a donor of a methyl group for methyl transferases
SAM will also produce SAH, when its methyl group is donated
SAH will repress the methyl transferases and is a competitive inhibitor of SAM
There is a figure to help explain this

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How does a high calorie diet lead to histone acetylation and life longevity? (2)

A

1) Metabolism of sugars and fats lead to formation of free radicals, also known as reactive oxygen species, ROS’s are dealt with using a special enzyme, but if this enzyme is depleted then the organism will have a shorter lifespan
2) Excess acetyl CoA due to greater metabolism, will reduce the abundance of heterochromatin, greater euchromatin, due to acetylation of histones in the cells, and with time cells will start aging faster due to higher calorie consumption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What happens when there is a mutation in Sir2, suppressors of NAD synthesis , and reduced vitamin B3?

A

Sir2 is a histone deacetylase which requires NAD to function, which means that a mutated Sir2 will result in the same shortening of life seen with the high calorie diet, because a mutation in Sir2 causes hyperacetylation of the histones, leading to more euchromatin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the features of young chromatin?

A

1) Compact
2) Stable nucleosomes
3) Low level of active histone modifications
4) High level of inactive histone modifications

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the features of old chromatin?

A

1) Open chromatin
2) Remodelled/ lost nucleosomes
3) High level of active histone modifications
4) Low level of inactive histone modifications

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How can heterochromatin help to distinguish between old and young cells?

A

Heterochromatin is more stable in younger cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What does an excess of sugar lead to? Why?

A

Premature aging, due to hyperacetylation, leading to formation of euchromatin, and a loss of heterochromatin, loss of heterochromatin suggests to the cell that it is aging

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How does cancer develop, in regards to the epigenetic landscape?

A

Develop when the epigenetic landscape of the cell has been altered, in addition to the accumulation of somatic mutations
There is less heterochromatin over the promoters of oncogenes, making them euchromatic, which means promoters are active, activating oncogenes leading to cancer.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How do epigenetic changes in mammals arise?

A

They can arise sporadically or be induced by the environment, due to toxins, nutrition and/or stress

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How does the intergenerational inheritance in exposed female mice work?

A

In the case of an exposed female mouse, if she is pregnant the fetus can be affected in utero (F1) as can the germline of the fetus (F2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the difference between intergenerational and trans generational inheritance in exposed females?

A

Intergenerational: Effects seen in F1 and F2 (first and second generation)
Transgenerational: Effects seen in F3 and onwards (third generation and onwards)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the idea of generational inheritance?

A

It is the idea that subsequent generations of an exposed parent, even though the child was not exposed has the effect that they were exposed
Exposure in F0 is being transmitted to progeny

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the difference between intergenerational and trans generational inheritance in exposed males?

A

Intergenerational: Effects seen in F1 (first generation)
Transgenerational: Effects seen in F2 and onwards (third generation and onwards)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What happens if the mother experiences stress during pregnancy?

A

The fetus also experiences stress
If the fetus is developing gremlin cells at the time of parental exposure, then this stress can lead to epigenetic marks that can be transmitted to the next 2 generations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What happens if the male experiences stress during spermatogenesis?

A

Stress will be transmitted to the next generation (only one generation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

How does the epigenetics of development and metabolism work?

A

The altered activity of chromatin modulating enzymes could have a significant impact on the differentiation of tissues in the developing embryos
Hence: if the mother is exposed to adverse conditions, the epi-genome of the future child will be altered
Sometimes, these adverse exposures of the pregnant mother can be passed to grandchildren and grand-grand children, which is known as epigenetic memory, the same can apply to fathers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the agouti gene? What is it dependent on?

A

Responsible for the synthesis of Phaeomelanin
The deposition of pigments in the hair by melanocytes depends on the activity of the Agouti gene (A)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What does the agouti gene do?

A

Oscilates between on and off, which means the gene cycles between active and inactive in the adult organism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What does the agouti gene produce when it is on? When it is off? What is the phenotype of the genes?

A

Agouti OFF: Black pigments are made
Agouti ON: Yellow pigments are made
Black is the recessive allele
Yellow is the dominant allele

30
Q

What happens if the agouti is constitutively on?

A

Well, it would be yellow and yellow mice are obese and prone to diabetes

31
Q

What happens in a wild type mouse with the Agouti gene?

A

Agouti expression oscillates
1) Oscillating OFF: BLACK
2) Oscillating ON: YELLOW,
so a single piece of hair has yellow and black stripes
3) Oscillating OFF: BLACk
So, the overall colour of the wild type mouse is brown

32
Q

Explain the different genotypes/phenotypes of the agouti mice

A

Agouti allele: Normal or Wildtype
Oscillating ON/OFF: Brown (agouti)
Agouti- (a): No functional protein made, so it is always OFF, meaning a is black
Ayellow (Ay): Oscillating doesn’t work, so always ON, meaning the mouse is yellow, obesity and diabetes
Avy allele: Oscilation works only in some cells

33
Q

What does the Avy allele contain? Be sure to describe it in detail

A

It contains a transposable element, IAP which is upstream of the Avy promoter
IAP is a transposon LTR, which means it has its own promoter
IAP has its own promoter that can override the normal oscillating Agouti promoter
The epigenetic state of the IAP promoter can determine the level of expression of the yellow pigment

34
Q

Explain the promoters in all agouti genes

A

Normal A allele (brown fur): The promoter alternates/oscilates between on and off
Mutant a allele (black fur): The promoter is always OFF
Mutant Ay allele (yellow fur): The promoter is always ON
Avy allele: The Avy contains an IAP, which has its own promoter, and the promoter can override the normal promoter. The IAP promoter only overrides the normal promoter in some cells and not others, which is what results in the patches of yellow fur and patches of brown fur, as such the normal promoter works in some cells, and not in others, and in ones where the IAP overrides, the normal promoter does not work.
The IAP overrides normal promoter to produce yellow coat when IAP promoter is unmethylated

35
Q

What is interesting about Avy mice?

A

Some Avy mice are yellow, some are brown, but most have brown and yellow patches
Hence, the Avy allele is in different states in genetically identical mice and within the cells of the same individual
All mice have the exact same genotype (Avy), but different phenotypes, (yellow, brown, agouti)

36
Q

How is it determined what phenotype is expressed in agouti cells? There is a diagram to help explain this

A

There are two potential epigenetic states of Avy that can occur within cells of Avy/a mice
First off all, the a allele is not functional, because agouti gene is mutated
The IAP which has a promoter, lies upstream of the agouti gene
If the IAP promoter is unmethylated, there is ectopic expression of the gene from the IAP, which results in a yellow coat colour
If the IAP promoter is methylated, this means that the gene is expressed under its normal development controls, leading to a brown coat colour.

37
Q

What were the steps in the dietary supplementation during pregnancy affect the coat colour of mice?

A

1) Cross Avy/a (male) with a recessive a/a female mice *2
2) Supplement diet with folic acid/VitB12: rich diet in one of the groups (abundance of SAM), leave other group with a normal diet
3)

38
Q

What was the experimental procedure for the dietary supplementation experiment?

A

Diets of female a/a mice are supplemented with methyl donating substances: folic acid, choline, vitamin B12 and give diet 2 weeks before mating with Avy/a males and throughout pregnancy and lactation

39
Q

What did the dietary supplementation during pregnancy affect the coat colour of mice reveal?

A

In the un-supplemented mother, there is less methylation of the IAP, leading to more yellow phenotypes
In the supplemented mother, there is plenty of SAM in the diet, which means IAP is more methylated here than in the normal diet, which produces more brown phenotypes
Therefore, the folic acid content in the mother’s diet leads to differential methylation of the IAP promoter in progeny, determining the coat colour.
It was seen that a folic acid/VitB12 rich diet reduces the frequency of yellow phenotypes, which suggests that exposure during pregnancy has epigenetic consequences for the progeny

40
Q

What does DNA methylation in agouti gene expression reveal?

A

Dietary supplements high in SAM lead to the IAP upstream of agouti gene to be more methylated than the mothers fed an unsupplemented diet,
More methylation:Brown
Less methylation: Yellow

41
Q

What is important about SAM?

A

SAM is a donor group of methyl, so when it gives methyl group, Mts can methylate histone/DNA which promotes formation of heterochromatin
So, therefore: building heterochromatin depends on the amount of SAM individuals have

42
Q

Explain genomic, non-genomic and altered cellular environment lead to the epigenetic reprogramming?

A

Genomic transmission and altered cellular environment do not have the potential for epigenome reprogramming, which means that they will not be transmitted to progeny
Non genomic transmission during development can be transmitted to progeny , leading to epigenome reprogramming, and therefore altered gene expression in progeny

43
Q

Explain the development of neurons

A

Development of neurons takes longer than the development of other tissues, so prolonged stress on the mother has a higher chance of affecting neuronal differentiation development
Neurons affect behaviour

44
Q

Can father’s pass on stress to sons? If so, how?

A

methylation of DNA in the sperm can transmit epigenetic marks to progeny, but not well understood

45
Q

How does paternal transmission occur? Why?

A

Paternal transmission of epigenetic defects to either sons or daughters can occur if an epimutation is introduced into the sperm epigenome in the form of altered DNA methylation or histone modification patterns on the nucleosomes that package the genomic DNA
Such alterations can be induced by aberrant genetic or environmental effects, and if the epimutations escape germline reprogramming, they can be transmitted to multiple subsequent generations, even in the absence of any further exposure to the original inducing effect

46
Q

How was the trans-generational inheritance of paternal traumatic exposure experiment set up?

A

Set up a male mice control group, male group exposed to acetophenone, and a male group exposed to propanol (aversion??)
Males were mated with naive females (no exposure)
Separate males from female
F1 offspring born and observe effects
Mate F1 males with naive females
F2 offspring born

47
Q

Why were the males separated from the females in paternal traumatic exposure experiment?

A

Removed so that behaviour of avoidance cannot be taught by males to progeny
To avoid teaching mice babies to avoid the smell
F1 progeny not taught behaviour by father

48
Q

What was observed in the F1 mice in the paternal traumatic exposure experiment?

A

In F1 whose fathers were exposed to actophenone, there was a strong aversion to the smell, suggesting trait was acquired as the behaviour was not taught.
In F1 whose fathers where exposed to propanol, there was a strong aversion to the smell, suggesting this trait was acquired as the behaviour was not taught
EPIGENETIC INHERITANCE!!

49
Q

How can we determine that aversion to smell is not genetic?

A

Looked at differential methylation of olfactory centre in the brain of these mice, to show behaviour is not genetic, but rather epigenetic because it is an accquired trait that cannot be explained by Mendelian genetics as fathers were not born with aversion trait

50
Q

What happened in the impaired DNA replication during embryonic development depresses a transgene array experiment?

A

If DNA replication is impaired, there is a loss of repression of the construct
Daf-21 drives expression of GFP in this construct (normally repressed)
Experiment was performed with licensing factors and DNA polymerases to produce progeny following a Mendelian distribution
If experiment is performed at 20 degrees in wildtype worms, worm is not very green
If experiment is performed at 20 degrees in mutant worms, worm is green
The worm is green because there is a loss of repression of Daf-21
If there is a loss of repression of Daf-21, heterochromatin cannot be maintained
Overall, worms with KO genes of replication factors are mated to mCHerry array worms
Replication deficiency lasts only during embryonal development
Impaired replication de-represses mCherry array

51
Q

Explain the DNA replication histone marks

A

DNA replication correlates to both H3K27me3 and H3K9me3
The transmission of H3K27me3 is dependent on DNA replication, and PRC2 catalyzes the methyl of H3K27
Behaviour correlates with the inability to maintain both epigenetic marks (H3K9me3 and H3K27me3)

52
Q

What is cancer associated with? What do we see?

A

Associated with mutations of cell cycle regulating genes in somatic cells
We observed genome instability and impaired DNA replication (mutations in checkpoints, p53, progression through damaged DNA, etc..)

53
Q

What plays a large role in cancer?

A

Epigenome plays a large role in cancer progression
In cancer, epigenetic aberrations, including methylation 100-1000, histone modifications > 1000, miRNA

54
Q

What did the streptomycin experiment show?

A

It shows genetic inheritance because the mutation that confers resistance to streptomycin was not acquired during exposure to streptomycin, it was spontaneous, so we need to mutate gene to see transmission

55
Q

What do neurons do?

A

Neurons engage in multiple connections via synapses
Avoid the generation of synapses with themselves, known as self-avoidance

56
Q

How is neuronal self-avoidance mediated?

A

In humans, by the Pcdh genes
The selection of the pcdh varian is epigenetically regulated
The selection involves the differential methylation of CTCF binding sites
The methylation of CTCF determines a complex 3D structure and the selection of the Pcdh variant
Pcdh genes have precise control over which neurons interact with other neurons (regulate cell to cell contact)

57
Q

What do neurons require?

A

A mechanism for self-recognition
Neurons need to recognize other neurons, cannot recognize themselves, so polycadherins make sure that neurons do not interact with themselves.

58
Q

How is the genome organized of clustered Pcdh genes?

A

alpha, beta, gamma clusters span a genomic region of 1 Mb
The alpha cluster has 12 monoallelically variable exon and two biallelically expressed variable exons (C1 and C2)
All variable exons splice to three constant expense that code for the intracellular region

59
Q

How is differential regulation of expression of alternate and c type promoters in the Pcdha gene cluster regulated?

A

Pcdhalpha alternate genes are expressed by long range DNA contacts between their promoters and the HS5-1 enhancer
These contacts are mediated by the CTCF and Cohesion protein complexes
The choice of Pcdha alternate promoters is also regulated by histone and DNA methylation (H3K9me3 and 5mC) and the activity of the Smcdh1 protein

60
Q

What is the relation between DNA methylation and promoter activation in the Pcdha cluster?

A

DNA methylation of CTCF binding sites and the DNA sequence between them, correlates with CTCF occupancy of CBS sites, engagement with HS5-1 enhancer, and transcriptional activation of the unmethylated promoter

61
Q

What is the summary of the epigenetic properties of Pcdh-alpha cluster?

A

Neuroblast cell expresses only three variable Pcdh-alpha exons
There are two CTCF binding sites at each active variable expense (CSE and eCBS sequences) at two at the HS5-1 enhancer (HS5-1a and HS5-1b)

62
Q

What are the summaries of the epigenetic properties of active and silenced pcdh-alpha on forming a 3D transcriptional hub, based on chromosome conformation capture?

A

Regions outside the central transcriptional hub are thought to be packaged in a repressive chromatin conformation
Suggested by the DNA methylation of in active pcdh-alpha promoter regions
Active genes are thought to be concentrated in a transcriptional hub, aided by a double clamp binding of CTCF, between the variable exons and the HS5-1 enhancer and cohesion

63
Q

How is alternate splicing dictated?

A

Methylation
Splices out exons downstream of chosen exon

64
Q

What did the transgenerational transmission of environmental information in C. elegans reveal?

A

It reveals that 14 generations display stress changes, even though all generations after the F0 were not exposed to the stress

64
Q

What did the transgenerational transmission of environmental information in C. elegans reveal?

A

It reveals that 14 generations display stress changes, even though all generations after the F0 were not exposed to the stress

65
Q

Explain mCHERRY

A

mCHERRY expresses red fluorescence, and when working red fluorescence will be seen
mCHERRY is repressed at 20 degrees Celsius

66
Q

What were the steps of the transgenerational transmission of C. elegans experiment?

A

In F0 generation, there was exposure to high temperature, 25 degrees celcius and this induced expression of mCHERRY
In F1 to F14, the temperature was decreased to 20 degrees celcius, but mCHERRY was still expressed, so there was abnormal expression even in the normal temperatures

67
Q

What was the summary of the transgenerational transmission of C. elegans experiment?

A

The worms contained cloned repressed mCHERRY array of genes
mCHERRY is normally repressed, but derepressed if the worm is grown at 25 degrees -
See epigenetic inheritance here because at 20 degrees mCHERRY is still expressed
Transmission occurs through oocytes and sperm and in cis with the locus

68
Q

What is important to note about the transgenerational transmission of C. elegans experiment?

A

PRC2 is not involved
Worms are grown at 25 degrees and then grown for 15 generations at 20 degrees
The de-repression of mCHERRY persists for 15 generations
Great example of a multigenerational epigenetic transmission in a model organism

69
Q

How was expression of mCHERRY determined?

A

FISH to detect expression
Looking for an overlap between mCHERRY and H3K9me phenotype associated with loss of H3K9me, because trait is not dependent on PRC2

70
Q

What is special about mCHERRY?

A

H3K9me3 is involved in mCHERRY exposure
Changes in H3K9me3 accompany de-repression and is transgenerationally inherited
The development at high temperature from embryo to adult results in reduced H3K9me3 on the array in the germline nuclei of adults

71
Q

What is special about H3K9me3?

A

H3K9me3 is depleted from transgene locus in F2 descendents of worms grown at 25 degrees celcius
F2 embryos were extracted
Reduced H3K9me3 on the array of germline nuclei of adults was extracted at moved from 16 degrees to 25 degrees during development and compared with worms kept constantly at 16 degrees celcius

MBG 4110 Final Exam (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions