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CREB-binding protein/p300 activates MyoD by acetylation
A Polesskaya1, A Duquet, I Naguibneva
1Laboratoire Oncogenèse, Différenciation et Transduction du Signal, CNRS UPR 9079, Institut Fédératif André Lwoff, 7 rue Guy Moquet, Villejuif, France.
The Journal of Biological Chemistry
|August 17, 2000
Summary
Myogenic factor MyoD acetylation by PCAF and CBP/p300 enzymes activates its function. This acetylation, occurring on specific lysines, is crucial for MyoD
Area of Science:
- Molecular Biology
- Epigenetics
- Muscle Development
Background:
- Myogenic factor MyoD is essential for muscle cell differentiation.
- Histone acetyltransferases CREB-binding protein (CBP)/p300 and PCAF are known regulators of MyoD.
- Previous studies suggested MyoD acetylation by PCAF enhances DNA binding.
Purpose of the Study:
- To investigate the role of MyoD acetylation in its functional activation.
- To identify the specific enzymes responsible for MyoD acetylation in vivo.
- To determine the functional consequences of MyoD acetylation on muscle promoter activity.
Main Methods:
- In vitro acetylation assays using purified MyoD and identified histone acetyltransferases.
- Analysis of MyoD acetylation status in muscle cells.
- Microinjection experiments to assess MyoD activity on muscle-specific promoters using wild-type and mutant MyoD.
Main Results:
- MyoD is constitutively acetylated in muscle cells.
- Both CBP/p300 and PCAF acetylate MyoD in vitro on two lysines at the DNA binding domain boundary.
- Acetylation by CBP/p300 and PCAF significantly increases MyoD activity on a muscle promoter; non-acetylated MyoD mutants show no activation.
Conclusions:
- MyoD acetylation is a critical functional activation mechanism.
- Both PCAF and CBP/p300 are key enzymes for MyoD acetylation in vivo.
- Acetylation enhances MyoD's ability to transactivate muscle-specific genes.