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LSM3235 - Epigenetics > Topic02 - Polycomb and Trithorax > Flashcards

Topic02 - Polycomb and Trithorax Flashcards

1
Q

Define the term “imprinted genes”

A

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.

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2
Q

Briefly suggest how genetic mutations can be affected by epigenetics

A

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

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3
Q

State whether PcG proteins are silencing or activating

A

Silencing

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4
Q

State whether TrxG proteins are silencing or activating

A

Activating

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5
Q

What are PcG and TrxG proteins?

A

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

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6
Q

What are HOX genes?

A

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

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7
Q

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

A

TRUE

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8
Q

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

A

PRC1 and PRC2 (Polycomb Repressive Complex)

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9
Q

State the key subunits of PRC2

A

EZH1 and EZH2

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10
Q

State the key subunits of PRC1

A

RING1A and RING1B

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11
Q

Briefly, what is the function of EZH1 and EZH2?

A

EZH1 and EZH2 are H3K27 methylases.

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

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12
Q

State the function of RING1A and RING1B

A

RING1A and RING1B confer H2AK119ub activity (E3 ubiquitin ligases)

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13
Q

State the two ways that PRC can be recruited

A
  1. unmethylated CpG islands

2. ncRNAs

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14
Q

What are CpG islands?

A

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

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15
Q

State the core components of PRC2

A

EZH1/2, EED, and SUZ12

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16
Q

State the core components of PRC1

A

RING1, CBX, PCGF, and HPH

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17
Q

State the accessory partners of PRC2

A

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

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18
Q

Briefly describe how PRC2 is recruited to CpG islands

A
  1. Accessory proteins of PRC2 first bind to unmethylated CpG islands.
  2. These accessory proteins then recruit PRC2 to CpG islands.
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19
Q

Give an example of an ncRNA that recruits PRC

A

HOTAIR serves as a guide ncRNA to recruit PRC2.

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20
Q

State the domain responsible for methylation activity in EZH subunits

A

SET domain

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21
Q

Describe the self-reinforcement of Polycomb repression

A
  1. EZH2 of the PRC2 complex catalyses H3K27me3 modification.

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

22
Q

State the component of PRC1 that recognises H3K27me3 marks

A

CBX2

23
Q

State the component of PRC2 that recognises H3K27me3 marks

A

EED

24
Q

State the three ways silencing is achieved by PRC1 and PRC2

A
  1. Chromatin compaction
  2. Holding of RNA Pol II
  3. SWI/SNF exclusion
25
Q

Briefly describe the cooperation of PRC1 and PRC2 in gene silencing

A

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

26
Q

State the enzyme responsible for copying parental DNA methylation marks

A

DNMT1 (maintenance DNMT)

27
Q

What is the difference between DNMT1 and DMNT3A/B?

A

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

28
Q

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

A

TRUE

29
Q

What are UTX and JMJD3?

A

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

30
Q

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

A

FALSE. JARID is an example of a demethylase.

31
Q

Briefly describe TrxG proteins.

A

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.

32
Q

What are COMPASS and COMPASS-like Trx complexes?

A

These are TrxG H3K4 methyltransferases.

33
Q

State the key subunit of the COMPASS complex.

A

SET1A/B

34
Q

State the role of SET1A/B

A

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

35
Q

State the key subunit of the COMPASS-like complex

A

MLL1/2/3/4

36
Q

State the role of MLL1 and MLL2

A

MLL1/2 function non-redundantly to impose H3K4me2/3.

These marks tend to be enriched on promoters and are associated with transcriptional activation.

37
Q

State the role of MLL3 and MLL4.

A

MLL3/4 are the major H3K4 monomethyltransferases in mammals.

These are associated with enhancers.

38
Q

State the role of ASH1

A

Imposes H3K36me3, a mark associated with active transcription elongation.

39
Q

What is ASH1?

A

ASh1 is a TrxG protein

40
Q

State the diseases associated with EZH2 loss of function

A

Weaver Syndrome, numerous cancers

41
Q

State the diseases associated with EZH1 loss of function

A

Diffuse large B cell lymphoma, follicular lymphoma

42
Q

State the diseases associated with MLL1

A

Wiedemann-Steiner syndrome, cancers

43
Q

State the diseases associated with MLL2

A

Kabuki syndrome, cancers

44
Q

State the diseases associated with MLL3

A

Autism, Kleefstra syndrome, cancers

45
Q

State the diseases associated with BAF complex

A

Neurological disorders, numerous cancers

46
Q

Give two examples of TrxG histone modifying complexes

A

COMPASS and COMPASS-like

47
Q

Give two examples of TrxG chromatin remodeling complexes

A

SWI/SNF and CHD

48
Q

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

A

SETA/B for COMPASS

MLLs for COMPASS-like

49
Q

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

A

Brg1 for SWI/SNF

50
Q

Define chromatin bivalency

A

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

51
Q

Bivalency is resolved during differentiation. TRUE or FALSE?

A

TRUE.

LSM3235 - Epigenetics (7 decks)

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