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Cancer - epigenetics > Epigenetics 3 > Flashcards

Epigenetics 3 Flashcards

1
Q

What is the test for a pluripotent cell?

A

Can form all 3 germ layers

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2
Q

What are the 3 germ layers?

A

Ectoderm, mesoderm, endoderm

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3
Q

What a progenitor cell?

A

A cell that proliferate but has restricted lineage

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4
Q

What are differentiated cells?

A

Post mitotic cell and so can no longer proliferate

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5
Q

What did waddingtons model imply?

A

That cells can not dedifferentiate - this is not the case

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6
Q

When did John Gurdon do his stuff?

A

1958 - tadpole somatic nucleus into xenopus occyte and made froggie

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7
Q

When was dolly the sheep?

A

1996

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8
Q

What Tf’s dedifferentiated somatic cells?

A

Oct3/4, KLF4, Sox2, c-MYC

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9
Q

What is used now instead of oncogenic c-Myc?

A

Tbx3

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10
Q

What are the epigenetic barriers for dedifferentiation?

A

DNA Methylation, chromatin modification

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11
Q

What intermediate was discovered that implicated that cytosines could be unmethylated?

A

5-hydroxymethylcytosine

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12
Q

What enzyme converts 5-methylcytosine to 5-hydroxymethylcytosine?

A

TET

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13
Q

What is the pathway from 5-methylcytosine –> carboxylcytosine?

A

5mC –> 5hmC –> formylcytosine –> carboxylcytosine

TET does all of it

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14
Q

What catalyses either formylcytosine or carboxylcytosine to Abasic site?

A

TDG

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15
Q

What occurs after Abasic formation?

A

Base excision repair

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16
Q

Other than base excision, how might carboxylcytosine be repaired to cytosine?

A

Decarboxylation - not comfirmed

17
Q

Are TET and TDG required for reprogramming cells?

A

yes

18
Q

What can replace in Oct4 in OSMK factors?

A

TET1

19
Q

What can neomorphic mutations in isocitrate dehydrogenase lead to?

A

Accumulation of 2-hydroxy-glutarate

20
Q

What are the downstream affects of 2-hydroxy-glutarate?

A

Inhibits TET and lysine demethylases (H3K9) - hence inhibits dedifferentiation
Can also inhibit succinate dehydrogenase ( causing build up of succinate and prevention of HIF hydroxylation, hence build up of HIF - oncogene)

21
Q

80% of adult glioma brain tumours have mutations in what?

A

Isocitrate dehydrogenase

Often no TET mutation are found - brain maybe relies more on chromatin structure??

22
Q

What do stem cells reexpress to adapt to microenvironment?

A

TET/IDH - a balancing act

23
Q

New therapies are often now designed to target specifically the cancer stem cells. What is an issue with this?

A

Cells can often develop resistance.

e.g. T cells were reprogrammed so they can recognise cancer antigens - cells eventually just lost antigen from surface

24
Q

How is MBDP used to prevent reprogramming as part of NuRD?

A

MBDP binds methyl groups on DNA and represses transcription

25
Q

WDR5 (in trithorax complex) binds Oct4 recruiting WDR5 to what kind of genes?

A

Pluripotent genes. This leads to methylation of H3K4 promoting gene activation

26
Q

How is UTX pro dedifferentiation?

A

It is a H3K27 demethylase which interacts with oct4, KLF4 and Sox2 to remove repressive mark H3M27me on pluripotency genes

27
Q

Is MYC necessary for reprogramming?

A

No, it just accelerates the process

28
Q

Which of the following in activating on the E-box promoter:

a) MAX-MAX
b) MYC-MAX
c) MAD-MAX

A

b) MYC-MAX

29
Q

How might MYC-MAX be a good drug target?

A

Drug might mimic interaction and therefore prevent interaction

30
Q

Is maintaining differentiation an active process?

A

Yes, we think so

31
Q

What do lineage specific guardians do?

A

Maintain differentiation

32
Q

What does lineage specific guardian Pax5 maintain?

A

B cells

33
Q

What does lineage specific guardian Lola maintain?

A

Immature neurons

Cancer - epigenetics (4 decks)

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