1st Feb - Chromatin Movers and Modifiers Flashcards
What are nucleosome remodelling complexes?
ATP dependent chromatin remodelling complexes use the energy obtained from ATP hydrolysis to alter the positioning, conformation and/or composition of nucleosomes, serving as chromatin remodelling engines
What are the key families of nucleosome remodelling complexes?
SWI/SNF family e.g. hSWI/SNF
ISWI family e.g. RSF
CHD1 family e.g. NuRD
What percentage of cancers is SWI/SNF mutated in?
30-40%
How do SWI/SNF complexes remodel chromatin?
Through the mobilization of nucleosomes both by sliding and the insertion/ejection of histone octamers
Who developed the histone code?
David Allis
How does methylation affect histone position?
Works as a docking site
What common domain detects Phospho-Y?
SH2 domain
What common domain detects Acetyl-K?
Bromodomain
What common domain detects Me3-K?
Chromodomains
What common domain detects polyUb-K?
UIM
Can histone modifications act as signalling?
Yes
Give an example where histones induce signalling
- Nuclear signal leads to histone acetylation
2. Signaling proteins with a bromodomain bind to the acetylated lysine such as SWI/SNF –> localised enzymatic activity
Can the same lysine on a histone tail be both acetylated and methylated?
NO, histone acetylation and methylation are mutually exclusive
What common domain primarily detects Me1/2 K?
PhD finger
How does H3K9 signal for heterochromatin?
H3K9 trimethylation is detected by a chromodomain(e.g. of HP1 which recruits Dnmt3a) –> DNA methylation
How does H3K9 signal for euchromatin?
H3K9 acetylation is detected by a bromodomain E.g. of P/CAF which is a HAT –> further acetylation
What determines cellular memory?
A balance between H3K4 and H3K27 methylation
Which proteins methylates H3K4me3 promoting gene transcription?
Trithorax group proteins
Which proteins methylates H3K27Me3 promoting gene repression?
Polycomb group proteins
Which protein within the Trithorax complex contains the SET domain?
MLL
What is the function of the Trithorax complex?
Adds three methyl groups to H3K4 and acetylates H3K27 promoting gene transcription
What is the function of the polycomb complex?
Trimethylate H3K27
Which protein within the Polycomb complex contains the SET domain?
EzH2
What is the function of a SET domain?
Contains methyltransferase activity
What are the two types of polycomb?
PRC1 and PRC2
What is the function of PRC2?
It works with EZh2 to add a methyl group to H3K27
What is the function of PRC1
It contains the CHD which reads H3K27 Me –> H2AK119 Ubiquitination
In Stem cells what are the defining histone modifications that indicate the genes are poised?
Having both H3K4me3 and H3K27me3 meaning that both polycomb and trithorax are present, so that if later the gene is switched on/off the other complex is removed accordingly
Which region of the histone is evolutionarily conserved?
The N-terminal region
What was the first histone modifying enzyme to be characterised?
Gin5
What is the half life of an acetyl modification?
A few minutes
