Brainscape's Knowledge GenomeTM

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


See full index

xGenomicss > The Epigenome > Flashcards

The Epigenome Flashcards

1
Q

What is the genome?

A
  • The complete set of genetic material in a cell
  • The DNA sequence that is present in a single full set of chromosomes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the nucleosome?

A

DNA will pack around the octamer core which is composed of 2 x H2A,H2B,H3,H4 and H1 histone inbetween.

This is then wound further

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

What is chromatin?

A

Is the combination of histones with DNA

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

What are the two types of chromatin?

A

Euchromatin -Gene rich, transcriptionally active, unique DNA sequence

Heterochromatin -Gene poor, less transcriptionally active, condensed, repetitive DNA sequence

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

What is the packing solution?

A
  • Nucleosomes are wound up to form 30nm fibres
  • Fibres are then wound up further with scaffold proteins to generate high order structures
  • Chromosomes are the most densely packed form of genomic DNA
  • Chromosomes are least accessible by transcription machinery - essentially heterochromatic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the epigenome?

What is an epigenetic change?

A
  • Sum of all heritable changes in the genome that do not occur in the primary DNA sequence and that affect gene expression
  • An epigenetic change results in a ‘change in phenotype but not in genotype’
  • Epigenetic marks allow for the regulation of the accessibility of DNA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Examples of epigenetic mechanisms

A
  • DNA methylation
  • Histone modification
  • X inactivation
  • Genomic imprinting
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is DNA methylation?

What enzyme catalyses DNA methylation?

What does it require?

A

Is the addition of a methyl group in the 5’ position of a cytosine

This is catalyse by DNA methyltransferase enzymes (DNMT1, DNMT3a and DNMT3b)

  • It requires S-Adenosyl Methionine to provide the methyl group
  • In differentiated cells it occurs in the CpG dinucleotides
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is DNA methylation catalysed by?

A

Catalysed by the DNA methyltransferase enzyme

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

What does DNA methylation require in order for the methyl group to be provided?

A

Requires S-adenosyl methionine to provide the methyl group

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

Where does DNA methylation in differentiated cells occur?

A

In differentiated cells, it occurs in CpG di-nucleotides

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

What catalyses DNA demethylation?

A

TET enzymes catalyse DNA demethylation

BER (base excision repair) alters the base further, the methyl group is removed completely to replace a normal carbon

Occurs via intermediates - there are important in regulating gene expression

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

How does DNA methylation affect gene expression?

A

-Turns transcription off by preventing the binding of transcription factors

  • DNA methylation patterns change during development and are an important mechanism for controlling gene expression
    • CpG islands are regions where the CpG concentration is higher
    • With methylation you cant bind T factors, polymerase isnt recruited, therefore you do not get gene expression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is histone modification?

A
  • Is the addition of chemical groups to the proteins that make up the nucleosome
  • Common modifications include acetylation + methylation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How are modifications named in histone modification?

A

Named based on the histone, the amino acid and the actual modification

  • For example, H3K4Me3 means that on Histone 3, the Lysine at position 4 is tri-methylated
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What do writer enzymes do and give examples?

A

Writers-Enzymes that add histone modification

Examples: -Histone acetyltransferase (HAT1) -Histone methyltransferase (EHMT1)

17
Q

What do eraser enzymes do and give examples?

A

Erasers-Enzymes that remove histone modification Examples: -Histone deacetylase -Histone demethylase

18
Q

What do reader enzymes do and give examples?

A

Readers-Enzymes that bind to the modification and alter gene activity

Examples:

  • Bromodomain and extra-terminal (BET) proteins – BRD2
  • Chromodomain proteins – CBX1
19
Q

What are the roles of histone modification?

A

Can repress or activate transcription depending on where the histone modification occurs

e.g Histone acetylation at lysine residues relaxes the chromatin (moves it away from heterochromatin to euchromatin) = makes accessible for T factors

Histone methylation more complex can repress or activate transcription depending on where it occurs

20
Q

What does acetylation at Lysine residue do?

A

Acetylation at Lysine residue relaxes the chromatin structure and makes it accessible for transcription factors

21
Q

How can histone modification occur and what can their effects do?

A

Can occur concurrently and so their effects can interact or modify each other

22
Q

What is X-inactivation?

A

Is the inactivation of one of the 2 X chromosome in every somatic cell in females

  • This is needed as the Y chromosome has no genes, so there is only one copy of each X chromosome gene in males (hemizygosity)

!!!!!!!!!!!!X-inactivation ensures that every somatic cell in all humans has the same number of active copies of every gene!!!!!!!!!!

23
Q

What is the process of X inactivation?

A
  1. The Xist gene is transcribed as a long non-coding RNA (IncRNA) from the x-inactivation centre (Xic) and binds all over the X chromosome
  2. Histone acetylation is removed and DNA and histone methylation occurs
  3. Inactive X chromosomes is heterochromatic
  • To stop both chromosomes from becoming inactive there is a mechanism to stop this from happening, one chromosome will produce a reverse sequence long coding RNA
    • Tsix is derived by transcription in the opposite direction and antagonises Xist RNA to keep one X active
24
Q

How is one X chromosome still kept active during X inactivation?

A

Tsix is derived by transcription in the opposite direction and antagonises Xist RNA to keep one X active

25
Q

What is genomic imprinting?

A

Is the selective expression of genes related to the parental origin of the gene copy

  • Every autosomal gene has one paternal and one maternal copy
  • Imprinted genes tend to be found in clusters
  • There are very few imprinted genes (~250)
26
Q

What is an example of X-inactivation?

A
  • All tortoiseshell cats are female
  • Tortoiseshell cats have one X with an orange fur allele and one X with a black fur allele
  • Random X-inactivation results in patches of orange and black fur
27
Q

How is genomic imprinting mediated?

A

Is mediated by imprinting control regions (ICRs)

28
Q

What is the process of genomic imprinting and what are essential to the process?

A

-One copy is silenced by DNA methylation, catalysed DMNT3a and histone methylation leading to inactivation -LNcRNAs are essential to the process

29
Q

What happens to imprinting patterns during gamete formation?

A

Imprinting patterns are reset during gamete formation

30
Q

Can we treat cancer by targeting epigenetic enzymes?

A
  • Global DNA methylation is altered in tumour cells
    • Hypermethylation of tumour suppressor genes
    • Hypomethylation of tumour activating genes
  • Epigenetic enzymes are often mutated in tumour cells
    • DNMT3A and TET1/2
    • Histone Acetyltransferases
    • Histone Methyltransferases
    • Histone Kinases
    • Histone Readers (acetyl/methyl/phosphoryl)
    • Histone Demethylases
31
Q

List some examples of pharmacoepigenetic drugs

A
  • DNA Methyl Transferase Inhibitors
    • 5-Azacytidine (Vidaza)

Treats Myelodysplastic syndrome (rare cancer)

  • Histone Deacetylase Inhibitors
    • Romidepsin (Istodax)

Treats Cutaneous T-cell lymphoma

These are succesful drugs for what we have so far gained knowledge in epigenetics

All the effects of gene expression might be directly affected by the environment. So the sequence is not changing but the epigenetic signals might change due to the chemicals you are exposed to which change gene expression - making you more suceptible/resistant to a disease

xGenomicss (20 decks)

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