Trigger 8: Basic epigenetics

Question 1

define what the epigenome is

Answer 1

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

Question 2

DNA determines

Answer 2

which mRNA is synthesises

Question 3

Epigenetic determines

Answer 3

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

Question 4

how can genes without mutations cause mutations

Answer 4

due to epigenetic editing increasing or decreasing gene expression

Question 5

epi means

Answer 5

above

Question 6

the epigenome control

Answer 6

gene accessibility

Question 7

the epigenome does not control

Answer 7

the genetic code

Question 8

Two main types of chemical modifications

Answer 8

• chemical modification of the genome

- histone modification

Question 9

genomic modification

Answer 9

through methylation and demethylation

Question 10

histone modification through

Answer 10

• acetylation
• deacetylation
• methylation
• phosphorylation

Question 11

epigenetic modifications act as switches

Answer 11

turning genes on/ off, decreasing/ increasing expression

Question 12

epigenetic explains why cells of identical phenotype end up as

Answer 12

neurones, muscle and skin

Question 13

why is the epigenome importnant

Answer 13

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

Question 14

different cell types are characterised by

Answer 14

different epigenomes

Question 15

haploid genome contains how many BP

Answer 15

3 billion (6 billion in diploid)

Question 16

all the base pairs are packaged into

Answer 16

23 chromosomes (46)

Question 17

DNA is complexed with

Answer 17

histones

Question 18

Nucleosomes consist of

Answer 18

8 histones around which DNA wraps 1.65 times

Question 19

DNA methylation involves the methylation of what

Answer 19

CpG islands

Question 20

CpG islands

Answer 20

parts of the genome rich in Cytosine and guanine

Question 21

C and G order

Answer 21

C must come before G

Question 22

which part of the CpG island is methylated

Answer 22

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

Question 23

Most cytosine methylation occurs in the sequence context

Answer 23

5‘-CG-3’

Question 24

when methyl is added to cytosine it becomes

Answer 24

5-methyl cytosine

Question 25

human genome is not

Answer 25

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

Question 26

% of 5-methylated cytosine found in the genome

Answer 26

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

Question 27

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

Answer 27

50%

Question 28

methylation within promoter regions correlates with

Answer 28

transcriptional silencing

Question 29

methylation dysregulates gene transcription through

Answer 29

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

Question 30

which enzymes catalyse methylation of CpG island

Answer 30

DNA methyl transferases

Question 31

DNA methyl transferases

Answer 31

DNMTs

Question 32

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

Answer 32

S-adenosyl methionine (SAM)

Question 33

when methyl is removed from SAM by DNMT it becomes

Answer 33

SAH

Question 34

SAH

Answer 34

S-adenosyl homocysteine

Question 35

Summary of DNA methylation

Answer 35

DNMT1 transfers methyl group from SAM to CpG island. SAM-->SAH

Question 36

which cytosine has methyl added

Answer 36

cytosine on 5th positiion

Question 37

when cytosine has methyl added it becomes

Answer 37

5 methyl cytosine

Question 38

therefore when lots of methylation of on CpG islands...

Answer 38

genes turned off due to TFs not being able to bind

Question 39

how many types of DNMTs

Answer 39

4

Question 40

methylation is an important mechanisms for

Answer 40

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

Question 41

which DNMT maintains normal patterns of methylation

Answer 41

DNMT1

Question 42

de novo methylation

Answer 42

when genes are turned off and cause disease

Question 43

which DNMTs are 'de novo methylases'

Answer 43

DNMT3a and DNMT3b

Question 44

DNMT1 requires a

Answer 44

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

Question 45

DNMT3a and DNMT3b

Answer 45

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

Question 46

DNMTs stand for

Answer 46

DNA MethylTransferases

Question 47

both establishment (DNMT3B) and maintenance (DNMT1) ae

Answer 47

crucial for development

Question 48

mice deficient in DNMT3B or DNMT1

Answer 48

embryonic lethal

Question 49

mice deficient in DNMT3a

Answer 49

die within 4 weeks

Question 50

DNMT1 important during

Answer 50

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

Question 51

5 hydroxy methyl cytosine (5hmC)

Answer 51

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

Question 52

How does 5hmC promote gene expression

Answer 52

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

Question 53

5mc

Answer 53

5 methyl cystosine

Question 54

5 methyl cytosine is produce by

Answer 54

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

Question 55

outline active demethylation cycle

Answer 55

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

Question 56

passive demethylation

Answer 56

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

Question 57

active demethylation

Answer 57

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