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Genomics SGUL Sem 3 > 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

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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 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

34
Q

What are inactive X chromosomes called?

A

Inactive X chromosomes are heterochromatic - Barr body

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 ability of a gene to be expressed depends upon the sex of the parent who passed on the gene
→ Functionally hemizygous - Willis syndrome

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
→ Catalyzed by DMNT3a and histone methylation leading to inactivation
→ Requires SAM which is involved in methylation reactions

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

45
Q

What is the role of histone readers?

A

Protein complexes that read combinations of marks: chromodomains specifically recognize methylated residues, while bromodomains bind acetylated residues

Genomics SGUL Sem 3 (21 decks)

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