1st Feb - Chromatin Movers and Modifiers

Question 1

What are nucleosome remodelling complexes?

Answer 1

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

Question 2

What are the key families of nucleosome remodelling complexes?

Answer 2

SWI/SNF family e.g. hSWI/SNF
ISWI family e.g. RSF
CHD1 family e.g. NuRD

Question 3

What percentage of cancers is SWI/SNF mutated in?

Answer 3

30-40%

Question 4

How do SWI/SNF complexes remodel chromatin?

Answer 4

Through the mobilization of nucleosomes both by sliding and the insertion/ejection of histone octamers

Question 5

Who developed the histone code?

Answer 5

David Allis

Question 6

How does methylation affect histone position?

Answer 6

Works as a docking site

Question 7

What common domain detects Phospho-Y?

Answer 7

SH2 domain

Question 8

What common domain detects Acetyl-K?

Answer 8

Bromodomain

Question 9

What common domain detects Me3-K?

Answer 9

Chromodomains

Question 10

What common domain detects polyUb-K?

Answer 10

UIM

Question 11

Can histone modifications act as signalling?

Answer 11

Yes

Question 12

Give an example where histones induce signalling

Answer 12

1. Nuclear signal leads to histone acetylation

2. Signaling proteins with a bromodomain bind to the acetylated lysine such as SWI/SNF –> localised enzymatic activity

Question 13

Can the same lysine on a histone tail be both acetylated and methylated?

Answer 13

NO, histone acetylation and methylation are mutually exclusive

Question 14

What common domain primarily detects Me1/2 K?

Answer 14

PhD finger

Question 15

How does H3K9 signal for heterochromatin?

Answer 15

H3K9 trimethylation is detected by a chromodomain(e.g. of HP1 which recruits Dnmt3a) –> DNA methylation

Question 16

How does H3K9 signal for euchromatin?

Answer 16

H3K9 acetylation is detected by a bromodomain E.g. of P/CAF which is a HAT –> further acetylation

Question 17

What determines cellular memory?

Answer 17

A balance between H3K4 and H3K27 methylation

Question 18

Which proteins methylates H3K4me3 promoting gene transcription?

Answer 18

Trithorax group proteins

Question 19

Which proteins methylates H3K27Me3 promoting gene repression?

Answer 19

Polycomb group proteins

Question 20

Which protein within the Trithorax complex contains the SET domain?

Answer 20

MLL

Question 21

What is the function of the Trithorax complex?

Answer 21

Adds three methyl groups to H3K4 and acetylates H3K27 promoting gene transcription

Question 22

What is the function of the polycomb complex?

Answer 22

Trimethylate H3K27

Question 23

Which protein within the Polycomb complex contains the SET domain?

Answer 23

EzH2

Question 24

What is the function of a SET domain?

Answer 24

Contains methyltransferase activity

Question 25

What are the two types of polycomb?

Answer 25

PRC1 and PRC2

Question 26

What is the function of PRC2?

Answer 26

It works with EZh2 to add a methyl group to H3K27

Question 27

What is the function of PRC1

Answer 27

It contains the CHD which reads H3K27 Me --> H2AK119 Ubiquitination

Question 28

In Stem cells what are the defining histone modifications that indicate the genes are poised?

Answer 28

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

Question 29

Which region of the histone is evolutionarily conserved?

Answer 29

The N-terminal region

Question 30

What was the first histone modifying enzyme to be characterised?

Answer 30

Gin5

Question 31

What is the half life of an acetyl modification?

Answer 31

A few minutes