Coactivator condensation drives cardiovascular cell lineage specification
Peiheng Gan1, Mikayla Eppert2, Nancy De La Cruz2
1Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Science Advances
|March 15, 2024
Summary
Myocardin (MYOCD) forms cellular condensates at specific concentrations, acting as a molecular switch for cell identity gene activation during cardiovascular development. This condensate formation is crucial for cell differentiation and reprogramming.
Area of Science:
- Molecular Biology
- Developmental Biology
- Cell Biology
Background:
- Cellular differentiation involves activating specific gene programs to determine cell lineage.
- The precise molecular mechanisms governing these cell fate decisions are not fully understood.
Purpose of the Study:
- To investigate the role of the cardiovascular transcriptional coactivator myocardin (MYOCD) in cell identity gene activation.
- To elucidate the mechanism by which MYOCD regulates gene expression during cell differentiation.
Main Methods:
- Investigated MYOCD's role in transcriptional condensate formation.
- Assessed the impact of MYOCD condensate formation on gene activation and cell reprogramming.
- Utilized protein region swapping to test the necessity and sufficiency of MYOCD's disordered region for condensate formation.
Main Results:
- MYOCD activates cell identity genes through concentration-dependent, switch-like formation of transcriptional condensates.
- Condensate formation occurs at critical concentration thresholds during smooth muscle cell and cardiomyocyte differentiation.
- The carboxyl-terminal disordered region of MYOCD is essential for condensate formation, gene activation, and cell reprogramming.
Conclusions:
- MYOCD-mediated transcriptional condensate formation is a critical requirement for gene activation in cardiovascular differentiation.
- This process acts as a molecular switch, driven by critical concentrations of cell type-specific regulators, to activate key developmental genes.
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