Epigenetics

Question 1

3 ways to end up with cardiac hypertrophy

Answer 1

1. High BP
2. Heart Attack
3. Genetic mutation

Question 2

How were mice used for models of cardiac hypertrophy?

Answer 2

Induced hypertrophy via pressure overload in mice by creating a Transverse Aortic Constriction (surgery)

Question 3

Hallmarks of Cardiac Hypertrophy

Answer 3

i. New protein synthesis
ii. Sarcomere assembly
iii. Gene Expression

Question 4

Definition of epigenetics

Answer 4

Reversible markers that can alter gene transcription without changing the underlying nucleotide sequence

Question 5

Most commonly modified AA on histone tails

Answer 5

Lysine

Question 6

How does ChIP work?

Answer 6

1. Isolate with formin
2. Fragment
3. Use Ab coupled with PCR to immunoprecipitate out desired sequence. The chromatin that is acetylated gets pulled down w/ Ab

Question 7

HAT vs HDAC

Answer 7

HAT = writer = activates gene
HDAC = eraser = deactivates gene

Question 8

How can you study protein function?

Answer 8

Gain of function via Transgenic overexpression
OR
Loss of function via KO and chemical inhibition

Question 9

HDAC9 does what to cardiac hypertrophy? How was it demonstrated?

Answer 9

Repressor of cardiac hypertrophy

Shown via HDAC9 knockdown leading to hypertrophy

Question 10

How do you block HDAC9?

Answer 10

Use small interfering RNA (siRNA) to block –> inhibits HDAC9 protein –> with added stress (TAC)= cardiomyocyte hypertrophy

Question 11

Overexpression of HDAC9 =?

Answer 11

block cardiomyocyte hypertrophy