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LSM3235 - Epigenetics > Topic03 - Heart Development > Flashcards

Topic03 - Heart Development Flashcards

1
Q

The mammalian heart is the first functional organ made during embryonic development. TRUE or FALSE?

A

TRUE.

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2
Q

All organisms lose the regenerative ability of the heart after birth. TRUE or FALSE?

A

FALSE. The teleost fish and urodeles have hearts that retain full regenerative ability in adults.

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3
Q

What causes scarring of the heart?

A

The deposition of extracellular matrix following heart injury

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4
Q

Briefly state the steps involved in heart formation

A
  1. Cardiac crescent
  2. Heart tube
  3. Looping heart
  4. Chamber formation
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5
Q

State the inductive signals involved in heart development

A

TGfb-Nodal, BMP, Wnt

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6
Q

State the key transcription factors involved in heart development

A

TBX5, GATA4, ISL1, NKX2.5

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7
Q

Briefly state the function of Baf60c

A

Baf60c is a subunit of the BAF chromatin remodeling complex that helps to coordinate the action of key cardiac TFs.

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8
Q

State the four main families of chromatin remodeling complexes

A
  1. SWI/SNF
  2. CHD
  3. ISWI
  4. INO80
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9
Q

Which family does BAF belong to?

A

SWI/SNF

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10
Q

What does BAF stand for?

A

Brg1/Brm-associated factor

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11
Q

Most chromatin remodeling complexes contain a subunit with ATPase activity. TRUE or FALSE?

A

FALSE. All of them have ATPase activity.

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12
Q

State the histone covalent modification-recognition domain of Brg1. Which modification does it recognise?

A

Brg1 has a bromodomain which recognises acetylated lysine residues.

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13
Q

Which domains recognise histone covalent modifications?

A

Bromo- and chromo- domains.

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14
Q

State the four different outcomes of SWI/SNF chromatin remodelling

A
  1. Repositioning
  2. Octamer ejection
  3. Unwrapping
  4. Dimer ejection
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15
Q

State the result of Brg-1 knockout in embryonic myocardial cells.

A

These cells will undergo premature differentiation.

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16
Q

How does Brg-1 maintain embryonic cardiomyocyte fate?

A

Brg1 interacts with other chromatin regulators such as HDACs to repress adult MHC and activate embryonic MHC.

17
Q

What does MHC stand for?

A

Myosin heavy chain

18
Q

State the adult MHC and embryonic MHC genes

A

MYH6 (adult)

MYH7 (embryonic)

19
Q

What is Tbx5?

A

Tbx5 is a key cardiac transcription factor important for normal heart development.

20
Q

What is the difference between direct reprogramming and indirect reprogramming?

A

Direct reprogramming involves trans-differentiation, while indirect reprogramming involves a pluripotent intermediate.

21
Q

State the factors required for direct reprogramming to heart tissue.

A

Baf60c, Gata4, Tbx

22
Q

Baf60c and Brg1 are subunits of the BAF complex. TRUE or FALSE?

A

TRUE.

23
Q

Define cardiac hypertrophy

A

The enlargement or thickening of heart muscle, a decrease in the size of the chambers of the heart, and a reduce capacity of the heart to pump blood to the tissues and organs around the body.

24
Q

Why does cardiac hypertrophy occur?

A
  1. Physiologically induced, via exercise.

2. Pathologically induced, which results in the re-expression of foetal heart gene programs (MYH7)

25
Q

State the role of Brg1 in cardiac hypertrophy.

A

Brg1 is abberantly upregulated, activating cardiac hypertrophy genes (cardiogenic) as well as embryonic genes (de-differentiation)

26
Q

Briefly describe Mhrt ncRNA

A

Mhrt ncRNA is transcribed antisense to MYH7 (embryonic MHC) and suppresses MYH7 expression

27
Q

Does Mhrt expression increase or decrease in adult hearts?

A

Increase

28
Q

Relate Brg1 to Mhrt

A

Brg1 causes the repression of Mhrt expression, thus lifting repression of embryonic MHC.

29
Q

State the role of Mhrt in rescuing cardiac hypertrophy

A

Overexpressing Mhrt can sequester Brg1, preventing it from activating embryonic MHC.

30
Q

How does Mhrt sequester Brg1?

A

Mhrt binds to the helicase domain of Brg1, displacing it from the chromatin (competitive inhibition).

31
Q

Brg1 preferentially binds to naked nucleic acid, hence binds to Mhrt easily. TRUE or FALSE?

A

FALSE. The Brg1 helicase domain preferentially binds to chromatinised DNA instead.

32
Q

State the two ncRNAs involved in heart development

A

Mhrt (Myheart) and Bvhrt (Braveheart)

33
Q

Briefly state the role of Bvhrt.

A

Bvhrt interacts with Suz12, a component of PRC2. PRC2 is then inhibited (decoy mechanism). Bivalency is resolved and cardiac gene expression is activated.
Bvhrt is required for cardiovascular lineage commitment.

LSM3235 - Epigenetics (7 decks)

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