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Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry
Published on: May 17, 2016
Cited3 activates Mef2c to control muscle cell differentiation and survival
Gnanapackiam Sheela Devakanmalai1, Hasan E Zumrut, Ertuğrul M Ozbudak
1Department of Genetics, Albert Einstein College of Medicine , Bronx, New York, NY 10461 , USA.
Biology Open
|June 22, 2013
Summary
Cited3 is a novel gene crucial for vertebrate muscle development. Its absence impairs muscle cell differentiation, growth, and survival, leading to immotility, while restoring Cited3 or mef2c rescues these defects.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Vertebrate muscle development relies on transcriptional regulators.
- Novel regulators at early myogenesis stages are key to understanding muscle formation.
- Zebrafish studies identified uncharacterized transcriptional regulators in early myogenesis.
Purpose of the Study:
- To investigate the function of the novel gene cited3 in myogenesis.
- To elucidate the role of cited3 within the muscle gene regulatory network.
- To determine the necessity of cited3 for muscle cell differentiation, growth, and survival.
Main Methods:
- Spatiotemporal microarray analysis in zebrafish.
- Antisense morpholino oligonucleotide knockdown of cited3 expression.
- Transplantation experiments to assess cell-autonomous and non-cell-autonomous functions.
- Protein truncation experiments to identify functional domains.
Main Results:
- Cited3 acts as a transcriptional coactivator downstream of Hedgehog signaling and myoD/myf5, but upstream of mef2c.
- Cited3 knockdown resulted in impaired muscle differentiation, growth, cell death, and immotility.
- Cited3 cell-autonomously activates mef2c in slow myofibers and non-cell-autonomously regulates fast myofiber genes.
- Restoring cited3 or mef2c expression rescued cited3 loss-of-function phenotypes.
Conclusions:
- Cited3 is essential for proper muscle cell differentiation and survival.
- The C-terminal domain of Cited3 is critical for its function, likely through interactions with histone acetylases.
- Cited3 plays a vital role in the gene regulatory network governing myogenesis.
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