Muscle Differentiation Flashcards
1
Q
What is the structure of Myogenic factors?
A
- Nuclear phosphoprotein
- Contains bHLH (Basic Helix-loop-helix) region
- Only 68 amino acids present in bHLH region necessary and sufficient for myogenic conversion of 10T1/2 cells
- This region present in all myogenic proteins.
2
Q
Function of Myogenic factors?
A
- Works as a dimer
- Binds to DNA 10x better as heterodimer with one of bHLH proteins encoded by E2 family of genes.
- HLH region required for dimerization with other proteins.
- Basic region required for DNA binding
- Two activation domains at each end
- Requires other factors to activate transcription.
3
Q
What are some examples of E2 family of genes?
A
E2A (E12, E47)
E2-2
HEB
4
Q
What other factor is needed by myogenic factors to activate transcription?
A
MEF2 transcription factor
5
Q
Function of MEF2
A
- Transcription factor
- Contains MADs and MEF domains
- Required for DNA binding and dimerization
- Does not possess myogenic activity alone, just enhances activity of MRFs
- Interacts with myogenic factors to regulate differentiation
- Also regulates the number of genes involved in differentiation.
6
Q
What is the DNA binding consensus sequence?
A
CANNTG - “E-Box”
7
Q
Transcription activation with MyoD
A
- MyoD complexes must bind to two or more upstream E-boxes
- If there are no E-boxes they are regulated by intermediate proteins like MEF2
- Activation Complex contains co-activators p300 and PCAF
- Highly specified binding to activate transcription.
- If placed on the wrong domain it will bind, and dimerize but not transcribe.
- MyoD intiates chromatin remodeling in regulatory regions of muscle-specific genes.
8
Q
Role of P300 and PCAF in the activation complex
A
- p300 Histone acetyltransferase
- Acetylated histones enhance transcription
- PCAF acetlyates MyoD at lysine residues near DNA-binding domain.
9
Q
A
