Epigenetics Flashcards

1
Q

Define epigenetics

A

Anything other than DNA used to control inheritance of genetic information.

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

Name four modes of genetic inheritance through epigenetics

A
  1. DNA methylation
  2. modification of histone proteins
  3. non-coding RNAs
  4. chromatin remodelling
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

At what location is DNA methylated?

A

At CpG

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

When are DNA methylation patterns established?

A

During embryo development, and are maintained by copying mechanisms during cell replication

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

Describe the writers of DNA methylation.

A

DNA methyltransferases: dnmt3a and dnmt3b perform de novo methylation, and dnmt1 performs maintenance methylation

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

What are CpG islands?

A

Short stretches of DNA in which the frequency of CpG methylation is higher.

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

Describe DNA hypo- and hypermethylation.

A

Hypomethylation: less methylation, more expression.

Hypermethylation: more methylation, less expression (txn factors cannot bind)

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

Define and describe the readers of DNA methylation.

A

These proteins have a conserved methyl-binding domain as well as a variable transcriptional repression domain.

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

What is MeCP2?

A

It regulates transcription as a reader of DNA methylation. Depending on the types of proteins that bind to it, it can both activate and supress gene expression in neurodevelopment.

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

What is Rett Syndrome?

A

It is a disorder caused by mutations in MeCP2 methylation reader. It is an X-linked neurodevelopment disorder.

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

Describe DNA methylation erasers.

A

They are involved in passive or active DNA demethylation and include the TET (ten-eleven translocation) family enzymes.

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

What is active DNA demethylation?

A

It involved three different enzymes to carry out DNA repair:

  1. methylcytosine is hydroxylated by TET to form hydroxymethylated cytosine
  2. methylcytosine is deaminated by AID to form methyluracil
    - these intermediates can be replaced with cytosine by BER
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are three roles for DNA methylation?

A
  1. gene silencing
  2. X-chromosome inactivation and genomic imprinting
  3. environmental factors induce epigenetic changes, leading to cancer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How does DNA methylation lead to cancer?

A
  • Hypomethylation results in genome instability
  • hypermethylation can silence tumor suppressor genes
  • methylation sites are hotspots for C->T transitions
  • methylation increases binding of chemical carcinogens and increase UV-induced mutations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How does methylation occur?

A

S-adenosyl methionine is formed by methionine and ATP and adds a methyl group to 5’ carbon of cytosine with the help of DNMTs.

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

What is the source of methyl groups for DNA methylation?

A
  • flavenoids and soft fruits and soya inhibit DNMT and could help reverse hypermethylation to tumor suppressor genes!
  • folates regulate methylation
  • diet during early development can cause lasting changes into adulthood.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How does BPA affect DNA methylation?

A

Mice fed BPA had unhealthy babies, but when supplemented with folate rich foods, the babies were born healthy.

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

How do father’s diets affect DNA methylation and epigenetics?

A

Food availability to paternal grandfathers at a young age affects the lifespan of his children.

Shortage of food = longer lifespan. More food = shorter lifespan and death by cardiovascular disease or diabetes.

Nutritional info about environment captured and passed onto next generations!

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

Describe the drastic role of DNA methylation in honeybees.

A
  • Queen been larvae feed on rolly jelly secreted by worker bees
  • queens are fertile and behave differently, while workers are sterile (over 550 genes affected)
  • both castes have same genome
  • a DNMT3 denovo patterning on larvae in a jelly-like manner caused them to develop into queens
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Compare and contrast maternal and paternal genomic imprinting.

A

Gene inherited from one parent is permanently inactivated and is passed on in this condition. Monoallelic inheritance.

  • maternal imprinting: allele from mother is inactive. only dad’s allele is expressed.
  • paternal imprinting: allele from father is inactive. only mom’s allele is expressed.
21
Q

On which chromosomes are most imprinted genes found?

A

Despite X-chromosome barr bodies, most imprinted genes are on the autosomes.

22
Q

Describe the inheritance of insulin-like growth factor 2 (Igf2) in mice.

A
  • only the paternal allele is expressed (mom’s is silenced)
  • inheritance of mutant maternal allele has no affect
  • if mutant paternal allele is inherited, mouse will experience dwarfing
23
Q

Describe the different histone subunits.

A

Histone core made of H2A, H2B, H3, H4. Linker is H1.

24
Q

How can histones hold large amounts of information?

A

There are about 44 lysines on the tails of histones that can possibly be acetylated!

25
Q

Name the types of histone modification.

A
  • acetylation
  • methylation
  • phosphorylation
  • ubiquitination
26
Q

Is euchromatin acetylated or deacetylated?

A

It is loosely packed, so it is highly acetylated.

27
Q

Is histone methylation activating or repressing?

A

It can be either, depending on the location and the context.

28
Q

What are the two main classes of HAT’s?

A
  1. nuclear
  2. cytoplasmic

specificities are defined in vitro

29
Q

Describe sex-linked histone acetylation and the experiment supporting it.

A
  • male rats left to self-administer cocaine or saline.
  • cocain-sired male rats developed cocaine resistant phenotype, but no affect on females
  • saline-sired males had normal histone acetylation levels
  • cocaine-fed males and their sons had elevated acetylation at Bdnf promotor causing higher Bdnf expression
30
Q

What is the effect of HDAC inhibitors?

A
  • can induce acetylation of histones
  • can inhibit tumor growth (tumor suppressor genes can remain expressed)

-

31
Q

Describe the role of readers in histone acetylation.

A

They bind acetylated lysine tails and recruit txn factors and chromatin organizers required for txn initiation and elongation,

32
Q

What is the goal of epigenetic editing?

A

Targeted overwrite of epigeneitc marks to modulate expression of selected target genes.

33
Q

What type of chromatin do embryonic stem cells have?

A

Fully open, ready for de novo epigenetic modification.

34
Q

What is the epigenome project?

A

It elicidates the relationship between genetic and epigenetic variation and its impact on health.

35
Q

What is the major challenge to epigenome mapping?

A
  • there is no single epigenome
  • each cell type has its own array of epigenetic marks
36
Q

Why should mother rats lick their babies?

A
  • highly nurtured pups grow up to be calm adults, nonlicked pups are anxious as adults
  • the difference is epigenetic and is stable into adulthood
  • shows epigenetic memory
37
Q

What types of noncoding RNAs are involved in epigenetics?

A

lncRNAs and miRNAs

38
Q

Define lncRNA

A

transcripts >200nt in length that do not contain ORFs capable of translating proteins.

39
Q

What is the evidence of lncRNA functionality?

A
  1. tissue and stage specific expression
  2. deregulated expression in disease
40
Q

What are the mechanisms of action of lncRNAs?

A
  1. chromatin remodeling
  2. regulation of RNA txn, splicing, editing, transport, translation, degradation, and compartmentalization
41
Q

What is the role of Xist in chromosome inactivation?

A

Xist mediates inactivation of female X chromosome. It coats the chromosome in cis, and is expressed only from the inactive X chromosome.

  • Xist recruits polycomb repressive complex 2 (PRC2)
  • PRC2 marks chromatin with repressive histone modifications
42
Q

What is the function of Tsix?

A

It is antisense to Xsist and serves as an antagonist of Xist expression. Its expression demarcates the active X chromosome.

43
Q

What is the role of miRNAs in epigenetics?

A

They regulate gene expression post-transcriptionally by binding 3’ UTR of specific mRNAs.

44
Q

How are miRNAs used as biomarkers?

A

extracellular miRNAs in blood, serum, plasma, saliva, and urine have been associated with various pathological conditions including cancer

45
Q

How are miRNAs not degraded in extracellular space?

A

They are delivered in exosomes to recipient cells.

46
Q

What are exosomes and when are they released?

A
  • Small extracellular vesicles
  • come from early endosomal pathway
  • inward budding of endosomal membrane gives rise to cytosolic multivesicular bodies
  • exosomes are released when MVBs fuse with the plasma membrane.
47
Q

What types of molecules are contained in exosomes?

A

proteins, lipids, mRNAs, miRNAs. lipid bilayer protects these things from degradation

48
Q

What are the steps of miRNA transfer by exosomes?

A
  1. miRNA packaging into exosomes and MVB formation
  2. exosome release from donor cell
  3. exosome uptake by acceptor cell
49
Q

How can exosomes be both good and bad?

A

They can deliver molecules such as prions that cause Alzheimer’s disease. They can also be used therapeutically by removing exosomes from a patient, loading them with a drug, and delivering back to patient for a higher immune system tolerance.