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Genomics (GEN501) > The Epigenome > Flashcards

The Epigenome Flashcards

1
Q

What is the genome?

A

→ The complete set of genetic material in a cell

→ DNA sequence present in a full set of chromosomes

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2
Q

What forms the first level of packing?

A

→ Histone proteins forming nucleosomes

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3
Q

What are the features of euchromatin?

A

→ Gene rich
→ transcriptionally active
→ nucleosomes are far apart

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4
Q

What are the features of heterochromatin?

A

→ Gene poor
→ less transcriptionally active
→ condensed appearance
→ repetitive DNA

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5
Q

Describe the packaging of DNA

A

→ Nucleosomes wound to make 30nm fibres
→ fibres wound up further with scaffold proteins
→ chromosomes are most densely packed

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6
Q

What is the epigenome?

A

→ the sum of all the heritable changes in the genome that do not occur in the primary DNA sequence that affect gene expression

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7
Q

What does an epigenetic change result in?

A

→ A change in the phenotype but not genotype

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8
Q

What are the 4 epigenetic mechanisms?

A

→ DNA methylation
→ histone modification
→ X inactivation
→ Genomic imprinting

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9
Q

What is DNA methylation and what does it require?

A

→ The addition of a methyl group in the 5’ position of cytosine
→ DNA methyltransferase
→ S-adenosyl methionine to provide the methyl group

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10
Q

How is DNA methylation done?

A

→ DNA methyltransferase enzymes

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11
Q

What are the DNA methyltransferase enzymes?

A

→ DNMT1
→ DNMT3a
→ DNMT3b

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12
Q

In differentiated cells where does DNA methylation occur?

A

→ in CpG nucleotides (C next to a G)

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13
Q

When does passive demethylation occur?

A

→ During replication

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14
Q

What is passive demethylation done by?

A

→ TET enzymes - ten eleven translocation enzymes

→ TDG - thymidine DNA glycosylase

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15
Q

What is the function of TET enzymes?

A

→ They catalyse the movement from 5 methylcytosine to hydroxy methyl cytosine to formyl to carboxy

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16
Q

What is the effect of DNA methylation?

A

→ Turns transcription off by preventing the binding of transcription factors

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17
Q

What is a CpG island?

A

→ A region of DNA where CpG is more frequent than normal

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18
Q

What is histone modification?

A

→ The addition of chemical groups to proteins that make up the nucleosome

19
Q

What are common histone modifications?

A

→ Acetylation and methylation

20
Q

What are modifications named based on?

A

→ Histone
→ amino acid
→ actual modification

21
Q

What does a H3K4Me3 mean?

A

→ on histone 3

→lysine at position 4 is trimethylated

22
Q

What are the three types of histone modification enzymes?

A

→ Writers
→ Erasers
→ Readers

23
Q

What are examples of 2 writer enzymes?

A

→ Histone acetyltransferase - HAT1

→ Histone methyltransferase - EHMT1

24
Q

What are 2 examples of eraser enzymes?

A

→ Histone deacetylase - HDAC1

→ Histone demethylase - KDM1

25
Q

What are 2 examples of reader enzymes?

A

→ Bromodomain and extra terminal (BET) proteins - BRD2

→ Chromodomain proteins - CBX1

26
Q

What is the effect of histone acetylation at lysine residues?

A

→ Relaxes the chromatin structure and makes it accesible to transcription factors

27
Q

Why does chromatin relax when acetyl is added at lysine residues?

A

→ Lysine is basic

→ if you add an acetyl (acid) group it relaxes the chromatin

28
Q

What is the effect of histone methylation?

A

→ Can repress or activate transcription depending on where it occurs

29
Q

How can histone modifications occur and what happens as a result?

A

→ at the same time (concurrently)

→ their effects can interact or modify each other

30
Q

Why does X inactivation occur?

A

→ ensures that every somatic cell in humans has the same number of active copies of every gene

31
Q

Why is X inactivation needed?

A

→ Y chromosome has virtually no genes

→ only one copy of X in males

32
Q

Describe how X inactivation occurs?

A

→ Xist gene is transcribed as long noncoding RNA from the X inactivation centre
→ It then binds all over the X chromosome
→ histone acetylation is removed and histone methylation occurs

33
Q

What are inactive X chromosomes called?

A

→ inactive X chromosomes are heterochromatic - Barr body

34
Q

What is Tsix and what does it do?

A

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

35
Q

Give an example of X inactivation in cats?

A

→ all tortoiseshell cats are female
→ they 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

36
Q

What is imprinting?

A

→ The selective expression of genes related to the parental origin of the gene copy

37
Q

Where do imprinted genes tend to be found?

A

→ in clusters

38
Q

What are imprinted genes mediated by?

A

→ Imprinting control regions

39
Q

What mechanism causes imprinting?

A

→ One copy is silenced by DNA methylation

→ catalysed by DMNT3a and histone methylation leading to inactivation

40
Q

When are imprinting patterns reset?

A

→ During gamete formation

41
Q

How are epigenetics altered in cancer cells?

A

→ hypermethylation of tumor suppressor genes

→ hypomethylation of tumor activating genes

42
Q

What enzymes are mutated in tumor cells?

A 
→ DNMT3a and TET1/2
→ Histone acetyltransferases 
→ Histone methyltransferases
→ Histone kinases
→ histone readers
→ histone demethylases
43
Q

What are 2 DNA methyltransferase inhibitors?

A

→ 5 azacytidine

→ Myelodysplastic syndrome

44
Q

What are 2 histone deacetylase inhibitors?

A

→ Romidepsin

→ Cutaneous T-cell lymphoma

Genomics (GEN501) (19 decks)

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