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(6-10) Translational Medical Science > Trigger 8: Basic epigenetics > Flashcards

Trigger 8: Basic epigenetics Flashcards

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Biology 101 flashcards USMLE® Step 1 flashcards
1
Q

define what the epigenome is

A

the REVERSIBLE regulation of gene expression, mediated primarily through changes in DNA methylation

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2
Q

DNA determines

A

which mRNA is synthesises

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3
Q

Epigenetic determines

A

how much mRNA is made, where and when it is synthesised

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4
Q

how can genes without mutations cause mutations

A

due to epigenetic editing increasing or decreasing gene expression

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5
Q

epi means

A

above

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6
Q

the epigenome control

A

gene accessibility

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7
Q

the epigenome does not control

A

the genetic code

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8
Q

Two main types of chemical modifications

A
  • chemical modification of the genome

- histone modification

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9
Q

genomic modification

A

through methylation and demethylation

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10
Q

histone modification through

A
  • acetylation
  • deacetylation
  • methylation
  • phosphorylation
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11
Q

epigenetic modifications act as switches

A

turning genes on/ off, decreasing/ increasing expression

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12
Q

epigenetic explains why cells of identical phenotype end up as

A

neurones, muscle and skin

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13
Q

why is the epigenome importnant

A

causes cellular differentiation during foetal development- meaning that although all cells have the same genome, they are not the same due to differences in the epigenome

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14
Q

different cell types are characterised by

A

different epigenomes

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15
Q

haploid genome contains how many BP

A

3 billion (6 billion in diploid)

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16
Q

all the base pairs are packaged into

A

23 chromosomes (46)

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17
Q

DNA is complexed with

A

histones

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18
Q

Nucleosomes consist of

A

8 histones around which DNA wraps 1.65 times

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19
Q

DNA methylation involves the methylation of what

A

CpG islands

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20
Q

CpG islands

A

parts of the genome rich in Cytosine and guanine

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21
Q

C and G order

A

C must come before G

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22
Q

which part of the CpG island is methylated

A

Addition of methyl group to C-5 position of cytosine residues.

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23
Q

Most cytosine methylation occurs in the sequence context

A

5‘-CG-3’

24
Q

when methyl is added to cytosine it becomes

A

5-methyl cytosine

25
Q

human genome is not

A

methylated uniformly- contains regions of unmethylated segments interspersed by methylated regions.

26
Q

% of 5-methylated cytosine found in the genome

A

4%- primarily at cytosine–guanine dinucleotides (CpGs)

27
Q

CpG islands (CpG rich regions) are found in how many promoter regions

A

50%

28
Q

methylation within promoter regions correlates with

A

transcriptional silencing

29
Q

methylation dysregulates gene transcription through

A

inhibition of transcription factor binding either directly or via altered histone acetylation

30
Q

which enzymes catalyse methylation of CpG island

A

DNA methyl transferases

31
Q

DNA methyl transferases

A

DNMTs

32
Q

where does the methyl group that DNMTs transfer to CpG island comes from

A

S-adenosyl methionine (SAM)

33
Q

when methyl is removed from SAM by DNMT it becomes

A

SAH

34
Q

SAH

A

S-adenosyl homocysteine

35
Q

Summary of DNA methylation

A

DNMT1 transfers methyl group from SAM to CpG island.

SAM–>SAH

36
Q

which cytosine has methyl added

A

cytosine on 5th positiion

37
Q

when cytosine has methyl added it becomes

A

5 methyl cytosine

38
Q

therefore when lots of methylation of on CpG islands…

A

genes turned off due to TFs not being able to bind

39
Q

how many types of DNMTs

A

4

40
Q

methylation is an important mechanisms for

A

maintaining gene expression e.g. when cells differentiate they will not use all of their genes

41
Q

which DNMT maintains normal patterns of methylation

A

DNMT1

42
Q

de novo methylation

A

when genes are turned off and cause disease

43
Q

which DNMTs are ‘de novo methylases’

A

DNMT3a and DNMT3b

44
Q

DNMT1 requires a

A

heme-methylated DNA substrate and will faithfully reproduce the pattern of DNA methylation on the newly synthesised strant

45
Q

DNMT3a and DNMT3b

A

all add methyl groups to CG dinucleotides which are previously unmethylated on both stands
- re-eastablish methylation patterns

46
Q

DNMTs stand for

A

DNA MethylTransferases

47
Q

both establishment (DNMT3B) and maintenance (DNMT1) ae

A

crucial for development

48
Q

mice deficient in DNMT3B or DNMT1

A

embryonic lethal

49
Q

mice deficient in DNMT3a

A

die within 4 weeks

50
Q

DNMT1 important during

A

DNA replication- to ensure DNA is methylated in the same places

51
Q

5 hydroxy methyl cytosine (5hmC)

A

is prevalent in embryonic stem cells and in the brain and plays a role in promoting gene expression

52
Q

How does 5hmC promote gene expression

A

conversion of 5mC (methylated cytosine- created by DNMTs) to 5hmC by TETs blocks repressive proteins that would typically be recruited to 4mc

53
Q

5mc

A

5 methyl cystosine

54
Q

5 methyl cytosine is produce by

A

DNMT

- Methyl group removed from SAM and added to cytosine on CpG islands

55
Q

outline active demethylation cycle

A

1) DNMT catalyses production of 5-mC from cytosine- repressing transcription and silencing genes
2) 5-mC is converted to 5hmC by TET, which then gets converted by another TET to 5-fC
3) 5-fc is converted to 5-caC
4) TDGBER convers 5-caC to cytosine

56
Q

passive demethylation

A

occurs due to absence of methylation of newly synthesised DNA strands by DNMT1 during several replication rounds

57
Q

active demethylation

A

mediated by multiple enzymes and can occur independent of DNA replication (TET and TDGBER)

(6-10) Translational Medical Science (40 decks)

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