Epigenetics 4 Flashcards

1
Q

What does too much stem cell self renewal cause?

A

Hyperplasia

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2
Q

What does too much stem cell differentiation cause?

A

Small organs

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3
Q

In asymmetric division, what do neural stem cells in drosophila divide to produce?

A

Self renew and ganglion mother cell

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4
Q

What is polarity in stem cell division?

A

Apical and basal alignment of protein during division

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5
Q

Does prospero align in the basal or apical cortex during asymmetrical division of stem cells?

A

Basal

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6
Q

What is DAM ID?

A

Attach DNA binding protein to E.coli enzyme which methylates adenine at GATC sites. Sites of methylated adenine indicate binding site of protein (e.g. prospero/lola)

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7
Q

What region of cyclin E gene does prospero bind?

A

introns

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8
Q

What did an RNA seq expression array reveal that prospero repressed?

A

neutral stem cell genes e.g. cyclin E

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9
Q

What happens to stem cells when prospero is knocked out?

A

Continuation of self renewal

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10
Q

What sequence was found conserved near prospero binding sites?

A

GATCG - binding site for lola

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11
Q

What binds the DNA sequence GATCG?

A

lola

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12
Q

What was used to identify lola as the DNA binding protein of sequence GATCG?

A

yeast 1 hybrid using His-3 marker protein

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13
Q

What is the structure of lola?

A

BTB zinc finger

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14
Q

What is the role of lola?

A

Transcription factor

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15
Q

What is the role of prospero?

A

Transcription factor

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16
Q

How many isoforms of lola were found?

A

25

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17
Q

How many isoform of lola that have zinc fingers were there?

18
Q

What kind of cell is lola expressed in?

A

Post mitotic neurons in drosophila

19
Q

Do most lola targets overlap with prospero targets?

20
Q

What is the function of lola?

A

To maintain a cell in a differentiated state by repressing neural stem cell genes. It also represses genes that have already been switched off by prosper

21
Q

What happened when MARCM was used to knock out lola in drosophila?

A

tumour formation because of dedifferentiation of cells

22
Q

Can removal of lola causes dedifferentiation of mature neurons?

A

No, this is controlled by other factors interacting with lola

23
Q

What was used to identify binding partners of lola?

A

yeast 2 hybrid screen - found over 100 hits

24
Q

Give example of factors that interact with lola to prevent dedifferentiation?

A

NuRD complex
Histone deacetylates
permanently repress even when lola is removed

25
What were 60% of lola hits from the yeast 2 hybrid screen?
lncRNAs
26
Is lncRNA segregated into GMC in the same way as prospero?
yes
27
What was lncRNA found to express?
micro-peptide 1
28
How many many amino acids in micro-peptide- 1?
30aa
29
What is the function of micro-peptide 1?
interacts with lola to prevent it from acting too early in differentiation
30
What is the hippo pathway?
Cascade that results in repression of Yorkie (YAP)
31
What does overexpression of yorkie (YAP) cause?
more proliferation of epithelium cells
32
What has been found up regulated in melloblastomas?
YAP
33
Yorkie causes symmetric division of stem cells. True or false?
True
34
What is the affect of hippo pathway on symmetrical divsion of stem cells?
inhibitory - blocks yorkie (YAP)
35
What is the notch pathway?
Delta ligand on one cell interacts with notch receptor on another. Causes gamma-secretase to cleave the intracellular region of notch (Rbpj) which translocates to the nucleus and promotes symmetrical division of stem cells
36
What is the affect of notch pathway on symmetrical divsion of stem cells?
promotes symmetrical division
37
Is notch a proto-oncogene?
yes
38
What is the affect of KO Rbpj?
more asymmetric division, reduced size of cortex
39
How does notch suppress growth?
different cellular context
40
Could gamma-secretase inhibitors be a potential theraputic?
yes