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?

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
State the role of Brg1 in cardiac hypertrophy.
Brg1 is abberantly upregulated, activating cardiac hypertrophy genes (cardiogenic) as well as embryonic genes (de-differentiation)
26
Briefly describe Mhrt ncRNA
Mhrt ncRNA is transcribed antisense to MYH7 (embryonic MHC) and suppresses MYH7 expression
27
Does Mhrt expression increase or decrease in adult hearts?
Increase
28
Relate Brg1 to Mhrt
Brg1 causes the repression of Mhrt expression, thus lifting repression of embryonic MHC.
29
State the role of Mhrt in rescuing cardiac hypertrophy
Overexpressing Mhrt can sequester Brg1, preventing it from activating embryonic MHC.
30
How does Mhrt sequester Brg1?
Mhrt binds to the helicase domain of Brg1, displacing it from the chromatin (competitive inhibition).
31
Brg1 preferentially binds to naked nucleic acid, hence binds to Mhrt easily. TRUE or FALSE?
FALSE. The Brg1 helicase domain preferentially binds to chromatinised DNA instead.
32
State the two ncRNAs involved in heart development
Mhrt (Myheart) and Bvhrt (Braveheart)
33
Briefly state the role of Bvhrt.
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.