Epigenetics 2

Question 1

What is a Trithorax complex?

Answer 1

A complex that interacts with chromatin - e.g. Brahma (SWI/SNF) complex

Question 2

What is the Brahma (SWI/SNF) complex?

Answer 2

An ATP dependent nucleosome remodelling complex that opens up chromatin.

Question 3

What is the catalytic core of the Brahma (SWI/SNF) complex?

Answer 3

Brahma or BRG1

Question 4

What does the interchangeable subunits of the SWI/SNF complex allow for?

Answer 4

Altered specificity.

Question 5

Does the SWI/SNF complex have a 3’-5’ or 5’-3’ nucleosome translocase ability?

Answer 5

3’-5’

Question 6

How can the SWI/SNF complex repress transcription?

Answer 6

Opens up the DNA and allows repressors to bind.

Question 7

Is the Brahma subunit a tumour suppressor?

Answer 7

Yes

Question 8

Is the SNF5 subunit a tumour suppressor? and if so why?

Answer 8

Yes - represses cyclin D1 expression, so is involved in cell cycle control.

Question 9

What does NuRD stand for?

Answer 9

Nucleosome remodelling and histone deacetylase complex

Question 10

What are the 2 core subunits of NuRD?

Answer 10

CHD3/4 (ATP dependent remodelling) and HDAC1/2

Question 11

Does the NuRD complex contain an MBD? and if so what does this allow it to do?

Answer 11

Yes - it can bind methylated DNA.

Question 12

What is NuRD complex recruited by?

Answer 12

TFs or methylated DNA.

Question 13

Can oncogenes recruit NuRD to repress tumour suppressors?

Answer 13

Yes

Question 14

What is the result of over-expression of MTA (NuRD subunit)?

Answer 14

Associated with EMT - causes metastasis.

Question 15

What is the transcription factor for MTA?

Answer 15

c-MYC

Question 16

What inhibits MTA?

Answer 16

p53

Question 17

Described briefly how miRNAs are processed by the cell.

Answer 17

Pri-miRNA hairpin loop is cleaved by Drosha and then exported out nucleus via exportin.
Dicer cuts in ~21nt strands and one of these is selected by Argonaute protein (RISC complex) to by gRNA –> inhibits specific mRNA expression.

Question 18

What happens if there is 100% sequence homology between miRNA and mRNA?

Answer 18

There is degradation of mRNA.

Question 19

What happens if there is NOT 100% sequence homology between miRNA and mRNA?

Answer 19

There is inhibition of translation

Question 20

What miRNA is activated by p53?

Answer 20

MIR34A

Question 21

What does onco-miRNA-21 do?

Answer 21

Inhibits PTEN

Question 22

What is the function of circular miRNAs?

Answer 22

They bind to miRNAs and store them for when they are needed rapidly.

Question 23

What is the size of lncRNA?

Answer 23

200bp-100kb

Question 24

What processes can lncRNA be involved in?

Answer 24

Chromatin remodelling, transcription co-activation/co-repression, protein-inhibition and splicing regulation.

Question 25

Describe what increased levels of HOTAIR causes.

Answer 25

Recruiting of PRC2 to specific gene promoters causing methylation of H3K27

Question 26

Describe what increased levels of p21 NAT causes.

Answer 26

This recruits Ago1 protein that methylates H3K27 near p21 gene - silencing it.

Question 27

Describe what increased levels of ANRIL causes.

Answer 27

ANRIL is transcribed antisense p15/ARF and forms a 2˚ structure and recruits CBX7, which in turn recruits PRC1 and silences the gene.

Question 28

What ncRNA expression is induced by DNA damage?

Answer 28

ncRNA cyclin D1 - causes conformational change in TLS protein that blocks CBP and p300 (HATs) binding cyclin D1 promoter.

Question 29

What is ncRNA cyclin D1 an example of?

Answer 29

A tumour suppressor ncRNA

Question 30

What are sORFs and where are they found?

Answer 30

These are small open reading frames (micro-peptides) in lncRNA.