Cardiac-enriched BAF chromatin-remodeling complex subunit Baf60c regulates gene expression programs essential for...

Area of Science:

• Molecular Biology
• Cardiovascular Biology
• Epigenetics

Background:

• Chromatin-remodeling complexes control organ-specific properties, but their mechanisms remain unclear.
• The cardiac-enriched BAF chromatin complex subunit, Baf60c (Smarcd3), has an incompletely understood role in heart development.

Purpose of the Study:

• To elucidate the function of Baf60c in cardiac development and function.
• To identify the molecular mechanisms by which Baf60c regulates cardiac gene expression.

Main Methods:

• Constitutive and conditional gene deletion of Baf60c in mouse models.
• Analysis of cardiac morphology, function, and gene expression.
• Yeast two-hybrid screening and co-immunoprecipitation to assess protein interactions.

Main Results:

• Loss of Baf60c resulted in embryonic cardiac hypoplasia and severe cardiac dysfunction.
• Conditional deletion in cardiomyocytes led to postnatal dilated cardiomyopathy and impaired contractility.
• Baf60c regulates genes involved in cardiac contractility, sarcomere function, and metabolism.
• Baf60c directly interacts with Myocardin (MYOCD), a key transcriptional co-factor.

Conclusions:

• Baf60c is essential for normal heart development and function.
• Baf60c coordinates a critical gene expression program for cardiomyocyte functional properties.
• The interaction between Baf60c and MYOCD is vital for regulating cardiac-specific gene networks.