Epigenetics 2 Flashcards
What is a Trithorax complex?
A complex that interacts with chromatin - e.g. Brahma (SWI/SNF) complex
What is the Brahma (SWI/SNF) complex?
An ATP dependent nucleosome remodelling complex that opens up chromatin.
What is the catalytic core of the Brahma (SWI/SNF) complex?
Brahma or BRG1
What does the interchangeable subunits of the SWI/SNF complex allow for?
Altered specificity.
Does the SWI/SNF complex have a 3’-5’ or 5’-3’ nucleosome translocase ability?
3’-5’
How can the SWI/SNF complex repress transcription?
Opens up the DNA and allows repressors to bind.
Is the Brahma subunit a tumour suppressor?
Yes
Is the SNF5 subunit a tumour suppressor? and if so why?
Yes - represses cyclin D1 expression, so is involved in cell cycle control.
What does NuRD stand for?
Nucleosome remodelling and histone deacetylase complex
What are the 2 core subunits of NuRD?
CHD3/4 (ATP dependent remodelling) and HDAC1/2
Does the NuRD complex contain an MBD? and if so what does this allow it to do?
Yes - it can bind methylated DNA.
What is NuRD complex recruited by?
TFs or methylated DNA.
Can oncogenes recruit NuRD to repress tumour suppressors?
Yes
What is the result of over-expression of MTA (NuRD subunit)?
Associated with EMT - causes metastasis.
What is the transcription factor for MTA?
c-MYC
What inhibits MTA?
p53
Described briefly how miRNAs are processed by the cell.
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.
What happens if there is 100% sequence homology between miRNA and mRNA?
There is degradation of mRNA.
What happens if there is NOT 100% sequence homology between miRNA and mRNA?
There is inhibition of translation
What miRNA is activated by p53?
MIR34A
What does onco-miRNA-21 do?
Inhibits PTEN
What is the function of circular miRNAs?
They bind to miRNAs and store them for when they are needed rapidly.
What is the size of lncRNA?
200bp-100kb
What processes can lncRNA be involved in?
Chromatin remodelling, transcription co-activation/co-repression, protein-inhibition and splicing regulation.
Describe what increased levels of HOTAIR causes.
Recruiting of PRC2 to specific gene promoters causing methylation of H3K27
Describe what increased levels of p21 NAT causes.
This recruits Ago1 protein that methylates H3K27 near p21 gene - silencing it.
Describe what increased levels of ANRIL causes.
ANRIL is transcribed antisense p15/ARF and forms a 2˚ structure and recruits CBX7, which in turn recruits PRC1 and silences the gene.
What ncRNA expression is induced by DNA damage?
ncRNA cyclin D1 - causes conformational change in TLS protein that blocks CBP and p300 (HATs) binding cyclin D1 promoter.
What is ncRNA cyclin D1 an example of?
A tumour suppressor ncRNA
What are sORFs and where are they found?
These are small open reading frames (micro-peptides) in lncRNA.
