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Published on: June 21, 2014
A dynamic role for HDAC7 in MEF2-mediated muscle differentiation
U Dressel1, P J Bailey, S C Wang
1University of Queensland, Institute for Molecular Bioscience, Centre for Molecular and Cellular Biology, Ritchie Research Laboratories, B402A, St. Lucia 4072, Queensland, Australia.
The Journal of Biological Chemistry
|March 30, 2001
Summary
Histone deacetylase 7 (HDAC7) directly inhibits MEF2 protein activity, impacting muscle differentiation. HDAC7
Area of Science:
- Molecular Biology
- Epigenetics
- Cellular Regulation
Background:
- Myocyte enhancer factor 2 (MEF2) proteins are crucial transcription factors in muscle development.
- Class II histone deacetylases (HDACs), including HDAC7, are involved in gene regulation.
- Overlapping expression patterns suggest a functional link between MEF2 and HDAC7.
Purpose of the Study:
- To investigate the functional interaction between MEF2 and HDAC7.
- To elucidate the mechanism by which HDAC7 regulates MEF2 activity.
- To understand the role of HDAC7 nucleocytoplasmic shuttling in myogenesis.
Main Methods:
- Glutathione S-transferase pulldown assays.
- Immunoprecipitation experiments.
- Analysis of protein-protein interactions and domain mapping.
Main Results:
- HDAC7 directly binds to MEF2 proteins (MEF2-A, -C, -D), inhibiting their transcriptional activity.
- MEF2 interaction with HDAC7 involves the MADS domain of MEF2 and the N-terminal repression domain of HDAC7.
- HDAC7 silencing of MEF2 is independent of its deacetylase activity and involves corepressor recruitment.
- Serum withdrawal induces myogenesis and causes HDAC7 translocation from the nucleus to the cytoplasm.
Conclusions:
- HDAC7 functions as a negative regulator of MEF2 activity, impacting muscle and heart tissue.
- The nucleocytoplasmic trafficking of HDAC7 is a key mechanism for regulating MEF2 targets during muscle differentiation.
- This interaction highlights a novel regulatory pathway in mammalian development and differentiation.
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