HDAC7 promotes cardiomyocyte proliferation by suppressing myocyte enhancer factor 2

Area of Science:

• Cardiovascular Biology
• Cellular and Molecular Medicine
• Regenerative Medicine

Background:

• Postnatal cardiomyocytes (CMs) lose proliferative capacity, limiting heart repair.
• Strategies to reactivate CM cell cycle have shown modest success.
• CM dedifferentiation may be necessary for proliferation.

Purpose of the Study:

• To investigate the role of histone deacetylase 7 (HDAC7) in postnatal cardiomyocyte proliferation.
• To explore HDAC7's mechanism in promoting CM dedifferentiation and cell cycle reentry.

Main Methods:

• Overexpression of Hdac7 in neonatal mouse cardiomyocytes.
• Analysis of CM dedifferentiation and proliferation markers.
• Investigation of transcription factor binding (MEF2, AP-1) and chromatin state.
• Assessment of HDAC7 interaction with minichromosome maintenance complex components.

Main Results:

• Hdac7 overexpression significantly induced CM dedifferentiation and proliferation.
• HDAC7 suppressed myocyte enhance factor 2 (MEF2), a key differentiation factor.
• Chromatin remodeling shifted from MEF2 binding (differentiation) to AP-1 binding (proliferation).
• HDAC7 interacted with minichromosome maintenance complex to promote cell cycle entry.

Conclusions:

• HDAC7 promotes cardiomyocyte proliferation through a dual mechanism of dedifferentiation and cell cycle activation.
• HDAC7 facilitates a switch in transcriptional programs favoring proliferation.
• HDAC7 represents a potential therapeutic target for heart regeneration and repair.