Brainscape's Knowledge GenomeTM

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


See full index

Developmental genetics and embyronal cancer > Epigenetic regulation > Flashcards

Epigenetic regulation Flashcards

1
Q

What is epigenetics? Give 3 examples?

A

altering of gene expression without changing the primary DNA structure
- DNA methylation
- histone modifications
- non-coding RNAs

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

What is the role of epigenetics in normal cells? Give 3 examples

A
  • the compartmentalisation of a complex genome into active and repressed regions
  • silencing of parasitic sequences
  • X inactivation
  • imprinting
  • mainly controlled by DNA methylation and histone modification
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the epigenome

A

the epigenetic code of the DNA

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

What is histone modification?

A

molecules attach to histone tails and affect chromatin condensation and DNAs ability to be transcribed

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

What is the basic mechanism underlying DNA methylation?

A
  • methyl groups added to cytosines make them into 5-methylcytosine
  • catalysed by DNMTs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How are methyl marks removed? how is it different to addition?

A
  • multiple steps and slower
  • TET enzymes drive multiple steps where the cytosine has multiple formations before going back to normal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How is DNA methylation controlled?

A
  • formed at gametogenesis and maintained through divisions
  • DNMT1 is a maintenance DNMT that maintains methyl marks
  • DNMT3A/B/L are de novo DNMTs that don’t require a template to add new methyl groups
  • TET genes involved in demethylation
  • KOs found role of DNMTs in mice that are embryonic lethal and alter methylation and imprintation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How can DNMTs be altered in cancer?

A
  • very rarely mutated
  • often overexpressed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Where does most DNA methylation occur in mammals?

A
  • at CpG islands (some non CpG especially in ESCs)
  • 50% of genes have them
  • stretches of DNA with CG content over 60%
  • usually demethylated and methylation is associated with cancer
  • non CpG methylation occurs in ESCs and not fully understood
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe a method that can be used to test for methylation

A
  • purify DNA and treat with bisulphide
  • unmethylated cytosines will be deaminated into uracils
  • methylated cytosines will remain to be measured
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Name 3 ways methylation inhibits transcription

A
  • directly causing steric hindrance and stopping TF binding
  • indirect effects via chromatin remodeling
  • boundary elements
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How can methylation affect chromatin to inhibit transription?

A

when methylation occurs, methyl-binding domain proteins can recognise methyl groups and complex with histone deacetylase proteins and deacetylase the histones, pulling the DNA closer to further repress transcription

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

What are boundary elements?

A
  • markers that help to control the boundaries between methylated and unmethylated regions
  • can affect the action of promoters
  • helps to regulate gene transcription
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How are histone modifications controlled?

A
  • change throughout development
  • marks are added and removed by enzymes such as HATs and HDACs
  • regulated by readers, writers and erasers
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Give an example of histone mark readers

A
  • bromodomains
  • recognise marks on the histones and signal for downstream TF and chromatin regulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Give an example of histone erasers

A
  • TETs perform demethylation
17
Q

Give an example of histone writers

A
  • HDACs, HATs
  • methyltransferases, demethylases
18
Q

What are the 2 possible mechanisms by which DNA methylation and histone modificatoin may interact?

A
  • DNA methylation driving histone modification
  • histone modification driving DNA methylation
  • evidence for both has been found
19
Q

How might DNA methylation direct histone modifications?

A
  • DNA methylated regions recruit methyl-CpG-binding proteins and histone deacetylase
  • this recruits histone methyltransferases that methylate the histones and stabilise the inactive chromatin
20
Q

How might histone modifications direct DNA methylation?

A
  • inactive chromatin undergoes DNA replication
  • histones recruit HP1 which recruits DNA methyltransferases to maintain DNA methylation throughout division
21
Q

Does histone methylation have activating or repressing effects?

A
  • both
  • H3K4 = activating
  • H3K9 or H3K27 = repressive
22
Q

How does DNA/histone methylation co-operation turn off pluripotency genes in development?

A
  • G9a histone methyltransferase induced H3K9me2
  • also recruits DNMTs to induce DNA methylation
23
Q

What are chromsome domains?

A
  • modular structures in chromatin that correlate with epigenetic marks
  • each have distinct tsructural and functional properties
  • for example polycomb domains control Hox gene silencing in drosophila
24
Q

How do epigenetic changes lead to X-inactivation

A
  • long non-coding RNA Xist binds the chromosome to be inactivated
  • DNA is highly methylated with repessive histone methyl marks too (H3K9me2, H4K27me3)
  • Xist can attract chromatin-modifying complexes such as polycomb to mediate inactivation
25
Q

How do epigenetic changes lead to inactivation of parasitic sequences?

A
  • 50% of the human genome is made of damaging repeats such as transposons that can insert into other genes
  • most 5-methylcytosine is found at these sites and transposon promoters are inactivated
  • prevents unwanted transcription
26
Q

What is genomic imprinting?

A
  • mule female horse, hinny female donkey - parental origin of genes are different
  • imprinted genes only express one allele
  • phenotype dependent on parental origin
  • resets on passage through the germline
27
Q

What is the life cycle of DNA methylation in imprinting ?

A
  • at the germline, de novo DNMTs add methyl marks
  • these are maintained through cell division by maintenance DNMTs
  • continues until gametogenesis where TETs remove methyl marks and new ones are applied
28
Q

What are the basic characteristics of imprinted genes?

A
  • only expressed on one allele
  • often in clusters with imprinting control regions within them
  • antisense and ncRNAs are common
  • different methylation patterns on each allele
29
Q

What are two human tumours that can arise from incorrect imprinting?

A
  • Wilm’s tumour from incorrect WT1 imprinting (leads to poor MET)
  • ovarian teratomas caused by lac of paternal imprinting
30
Q

Give an example of a genomic imprinting locus.

A
  • IGF2 encodes fetal growth factor and is only expressed on the paternal allele
  • H19 encodes an untranslated RNA that appears to act as a tumour suppressor and is only expressed on the maternal allele
31
Q

How do IGF2 and H19 interact in genomic imprinting on the paternal allele?

A
  • on the paternal allele the IGF2 promoter interacts with an enhancer downstream of H19
  • extensive DNA methylation of the boundary element between IGF2 and H19 means that CTCF cant bind and this can happen
  • 2 alleles like this can lead to wilms tumour
32
Q

How do IGF2 and H19 interact in genomic iprinting on the maternal allele?

A
  • no hypermethylation of the boundary element
  • CTCF can bind here and create a boundary that stops the IGF2 promoter from accessing the promoter
  • allows H19 to use it instead
  • two alleles like this can lead to dwarfism
33
Q

What are epimutations?

A
  • mutations that can interfere with the loss of boundary elements
  • seen in Wilm’s tumour if IGF2 is overexpressed on both alleles
  • mutation that enhances the boundary element instead has 2 H19 alleles and leads to growth failure - silver-russell dwarfism)
34
Q

What are two theories on why genomic imprinting evolved?

A

Haig theory - imporinting lessens conflict between patnerla and maternal genomes by allowing a mixture to be expressed
Barlow theory - methylation developed as a defense against foreign DNA and was evolved for control of development

Developmental genetics and embyronal cancer (17 decks)

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