Deacetylase-dependent and -independent role of HDAC3 in cardiomyopathy

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Updated: Aug 11, 2025

Assays for Validating Histone Acetyltransferase Inhibitors
09:11

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

6.6K

Jieyu Ren1, Qun Zeng1, Hongmei Wu1

  • 1Department of Biochemistry and Molecular Biology, College of Hengyang Medical, University of South China, Hengyang, China.

Journal of Cellular Physiology
|February 6, 2023
PubMed

Insights

Histone deacetylase 3 (HDAC3) maintains cardiac contractility and prevents fibrosis through both enzymatic and nonenzymatic roles. Its deacetylase-independent functions are crucial for heart function, while its enzymatic role regulates triglyceride levels.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Genetics

Background:

  • Cardiomyopathy impairs cardiac function.
  • Histone deacetylase 3 (HDAC3) has known deacetylase functions and potential nonenzymatic roles.
  • The specific molecular functions of HDAC3 in cardiomyopathy are not fully understood.

Purpose of the Study:

  • To investigate the enzymatic and nonenzymatic roles of HDAC3 in cardiomyopathy using a Drosophila model.
  • To elucidate the molecular mechanisms underlying HDAC3's function in cardiac health.

Main Methods:

  • Utilized Drosophila as a genetic model organism.
  • Performed cardiac-specific HDAC3 knockdown (KD).
  • Employed immunohistochemistry to analyze cardiac structure and protein deposition.
  • Assessed whole-body triglyceride levels and cardiac fibrosis.

Main Results:

  • Cardiac-specific HDAC3 KD resulted in prolonged systoles, reduced cardiac contractility, and myofiber disruption.
  • HDAC3 KD hearts exhibited increased whole-body triglycerides and fibrosis.
  • Deacetylase-dead HDAC3 mutants rescued contractility and Pericardin deposition but not triglyceride accumulation in HDAC3 KD hearts.

Conclusions:

  • HDAC3 plays a deacetylase-independent role in maintaining cardiac contractility and preventing Pericardin deposition.
  • HDAC3 has a deacetylase-dependent role in maintaining triglyceride homeostasis.
  • These findings highlight the multifaceted roles of HDAC3 in cardiac function and disease.

Keywords:
DrosophilaPericardincardiac contractilitycardiomyopathydeacetylasefibrosistriglycerides

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