Topic02 - Polycomb and Trithorax

Question 1

Define the term “imprinted genes”

Answer 1

Imprinted genes are genes whose expression is determined by the contributing parent. In imprinted genes, only one of the two copies are normally turned on.

Question 2

Briefly suggest how genetic mutations can be affected by epigenetics

Answer 2

Epigenetics can influence the level of expression of DNA repair machinery.
Alternatively, epigenetics can also control the accessibility of impaired DNA to DNA repair machinery

Question 3

State whether PcG proteins are silencing or activating

Answer 3

Silencing

Question 4

State whether TrxG proteins are silencing or activating

Answer 4

Activating

Question 5

What are PcG and TrxG proteins?

Answer 5

These are a heterogenous collection of chromatin proteins that maintain silenced or activated gene expression states respectively.

Question 6

What are HOX genes?

Answer 6

HOX genes are a family of developmental control genes, encoding for transcription factors that control the body plan.

Question 7

PcG/TrxG epigenetic marks are heritable across cell divisions. TRUE or FALSE?

Answer 7

TRUE

Question 8

State the two major multiprotein complexes in which PcG proteins are found

Answer 8

PRC1 and PRC2 (Polycomb Repressive Complex)

Question 9

State the key subunits of PRC2

Answer 9

EZH1 and EZH2

Question 10

State the key subunits of PRC1

Answer 10

RING1A and RING1B

Question 11

Briefly, what is the function of EZH1 and EZH2?

Answer 11

EZH1 and EZH2 are H3K27 methylases.

EZH2 is the predominant enzyme that catalyses H3K27 di/trimethylation.

Question 12

State the function of RING1A and RING1B

Answer 12

RING1A and RING1B confer H2AK119ub activity (E3 ubiquitin ligases)

Question 13

State the two ways that PRC can be recruited

Answer 13

1. unmethylated CpG islands

2. ncRNAs

Question 14

What are CpG islands?

Answer 14

CpG islands are regions of the genome that contain a large number of CG dinucleotide repeats.
CpG islands tend to be enriched within or near promoters.
CpG islands tend to resist DNA methylation

Question 15

State the core components of PRC2

Answer 15

EZH1/2, EED, and SUZ12

Question 16

State the core components of PRC1

Answer 16

RING1, CBX, PCGF, and HPH

Question 17

State the accessory partners of PRC2

Answer 17

JARID2, AEBP2, and PCLs (Polycomb-like proteins)

Question 18

Briefly describe how PRC2 is recruited to CpG islands

Answer 18

1. Accessory proteins of PRC2 first bind to unmethylated CpG islands.
2. These accessory proteins then recruit PRC2 to CpG islands.

Question 19

Give an example of an ncRNA that recruits PRC

Answer 19

HOTAIR serves as a guide ncRNA to recruit PRC2.

Question 20

State the domain responsible for methylation activity in EZH subunits

Answer 20

SET domain

Question 21

Describe the self-reinforcement of Polycomb repression

Answer 21

1. EZH2 of the PRC2 complex catalyses H3K27me3 modification.

2. H3K27me3 is then recognised by the EED subunit, which allosterically activates EZH2 enzymatic activity.

Question 22

State the component of PRC1 that recognises H3K27me3 marks

Answer 22

CBX2

Question 23

State the component of PRC2 that recognises H3K27me3 marks

Answer 23

EED

Question 24

State the three ways silencing is achieved by PRC1 and PRC2

Answer 24

1. Chromatin compaction
2. Holding of RNA Pol II
3. SWI/SNF exclusion

Question 25

Briefly describe the cooperation of PRC1 and PRC2 in gene silencing

Answer 25

PRC2 first catalyses H3K27me3. This mark is then recognised by the CBX2 subunit of PRC1, which leads to gene repression.

Question 26

State the enzyme responsible for copying parental DNA methylation marks

Answer 26

DNMT1 (maintenance DNMT)

Question 27

What is the difference between DNMT1 and DMNT3A/B?

Answer 27

DNMT1 has a preference for hemi-methylated CpG, while DMNT3A/B methylates both hemi-methylated and unmethylated CpG at the same rate

Question 28

PRC2-H3K27me3 can be transmitted across cell divisions. TRUE or FALSE?

Answer 28

TRUE

Question 29

What are UTX and JMJD3?

Answer 29

These are specific H3K27 di- and tri-methyl demethylases.

Question 30

PRC2 accessory partners do not contain demethylases. TRUE or FALSE?

Answer 30

FALSE. JARID is an example of a demethylase.

Question 31

Briefly describe TrxG proteins.

Answer 31

TrxG proteins are a heteregenous collection of proteins responsible for maintaining active gene expression. These proteins are either histone-modifying complexes or chromatin-remodelling complexes.

Question 32

What are COMPASS and COMPASS-like Trx complexes?

Answer 32

These are TrxG H3K4 methyltransferases.

Question 33

State the key subunit of the COMPASS complex.

Answer 33

SET1A/B

Question 34

State the role of SET1A/B

Answer 34

SET1A/B are the central H3K4 di-/tri-methyltransferase that play a default global H3K4me2/3 activity in mammalian cells.

Question 35

State the key subunit of the COMPASS-like complex

Answer 35

MLL1/2/3/4

Question 36

State the role of MLL1 and MLL2

Answer 36

MLL1/2 function non-redundantly to impose H3K4me2/3. | These marks tend to be enriched on promoters and are associated with transcriptional activation.

Question 37

State the role of MLL3 and MLL4.

Answer 37

MLL3/4 are the major H3K4 monomethyltransferases in mammals. | These are associated with enhancers.

Question 38

State the role of ASH1

Answer 38

Imposes H3K36me3, a mark associated with active transcription elongation.

Question 39

What is ASH1?

Answer 39

ASh1 is a TrxG protein

Question 40

State the diseases associated with EZH2 loss of function

Answer 40

Weaver Syndrome, numerous cancers

Question 41

State the diseases associated with EZH1 loss of function

Answer 41

Diffuse large B cell lymphoma, follicular lymphoma

Question 42

State the diseases associated with MLL1

Answer 42

Wiedemann-Steiner syndrome, cancers

Question 43

State the diseases associated with MLL2

Answer 43

Kabuki syndrome, cancers

Question 44

State the diseases associated with MLL3

Answer 44

Autism, Kleefstra syndrome, cancers

Question 45

State the diseases associated with BAF complex

Answer 45

Neurological disorders, numerous cancers

Question 46

Give two examples of TrxG histone modifying complexes

Answer 46

COMPASS and COMPASS-like

Question 47

Give two examples of TrxG chromatin remodeling complexes

Answer 47

SWI/SNF and CHD

Question 48

Give an example of a key subunit of TrxG histone modifying complexes

Answer 48

SETA/B for COMPASS | MLLs for COMPASS-like

Question 49

Give an example of a key subunit of TrxG chromatin remodeling complexes

Answer 49

Brg1 for SWI/SNF

Question 50

Define chromatin bivalency

Answer 50

The state in which both activating and silencing marks are present on the chromatin.

Question 51

Bivalency is resolved during differentiation. TRUE or FALSE?

Answer 51

TRUE.