Histone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish

Bühler, Anja; Gahr, Bernd M.; Park, Deung-Dae; Bertozzi, Alberto; Boos, Alena; Dalvoy, Mohankrishna; Pott, Alexander; Oswald, Franz; Kovall, Rhett A.; Kühn, Bernhard; Weidinger, Gilbert; Rottbauer, Wolfgang; Just, Steffen

doi:10.1371/journal.pgen.1009890

Cited by 7 publications

(12 citation statements)

References 46 publications

(61 reference statements)

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“…Moreover, acetylation of vestigial-like 4 (VGLL4) at K225 by P300 negatively regulates its binding to the transcription factor TEA Domain Transcription Factor 1 (TEAD1), leading to decreased neonatal cardiomyocytes proliferation and cardiomyocytes necrosis [ 20 ]. Inhibition of HDAC1 was also described to decrease the proliferation cardiomyocyte in zebrafish [ 49 ]. Indeed, mutation in HDAC1 gene that induces protein instability is associated with decreased cardiomyocyte proliferation, suggesting an important role of HDAC1 during heart growth [ 49 ].…”

Section: Cardiac Acetylationmentioning

confidence: 99%

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Cardiac Acetylation in Metabolic Diseases

et al. 2022

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Lysine acetylation is a highly conserved mechanism that affects several biological processes such as cell growth, metabolism, enzymatic activity, subcellular localization of proteins, gene transcription or chromatin structure. This post-translational modification, mainly regulated by lysine acetyltransferase (KAT) and lysine deacetylase (KDAC) enzymes, can occur on histone or non-histone proteins. Several studies have demonstrated that dysregulated acetylation is involved in cardiac dysfunction, associated with metabolic disorder or heart failure. Since the prevalence of obesity, type 2 diabetes or heart failure rises and represents a major cause of cardiovascular morbidity and mortality worldwide, cardiac acetylation may constitute a crucial pathway that could contribute to disease development. In this review, we summarize the mechanisms involved in the regulation of cardiac acetylation and its roles in physiological conditions. In addition, we highlight the effects of cardiac acetylation in physiopathology, with a focus on obesity, type 2 diabetes and heart failure. This review sheds light on the major role of acetylation in cardiovascular diseases and emphasizes KATs and KDACs as potential therapeutic targets for heart failure.

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Section: Cardiac Acetylationmentioning

confidence: 99%

“…Inhibition of HDAC1 was also described to decrease the proliferation cardiomyocyte in zebrafish [ 49 ]. Indeed, mutation in HDAC1 gene that induces protein instability is associated with decreased cardiomyocyte proliferation, suggesting an important role of HDAC1 during heart growth [ 49 ].…”

Section: Cardiac Acetylationmentioning

confidence: 99%

Cardiac Acetylation in Metabolic Diseases

et al. 2022

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“…This Brg1 gene was specifically found to regulate HDAC mechanisms through development [ 73 ]. In zebrafish, it has been found that the histone deacetylates 1 (HDAC1) is conserved in zebrafish and plays a vital role in the regeneration and proliferation of cardiomyocytes similar to that of neonatal and embryonic mammalian cardiomyocytes [ 74 ]. Finally, it has been observed that by inhibiting HDACs, such as HDAC2, has helped with cardiac repair after injury by specifically inhibiting increased cardiac cell autophagy [ 75 ].…”

Section: Epigenetic Regulation Of Cardiomyocytes Through Developmentmentioning

confidence: 99%

Targeting Epigenetic Regulation of Cardiomyocytes through Development for Therapeutic Cardiac Regeneration after Heart Failure

Kraus

2022

IJMS

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Cardiovascular diseases are the leading cause of death globally, with no cure currently. Therefore, there is a dire need to further understand the mechanisms that arise during heart failure. Notoriously, the adult mammalian heart has a very limited ability to regenerate its functional cardiac cells, cardiomyocytes, after injury. However, the neonatal mammalian heart has a window of regeneration that allows for the repair and renewal of cardiomyocytes after injury. This specific timeline has been of interest in the field of cardiovascular and regenerative biology as a potential target for adult cardiomyocyte repair. Recently, many of the neonatal cardiomyocyte regeneration mechanisms have been associated with epigenetic regulation within the heart. This review summarizes the current and most promising epigenetic mechanisms in neonatal cardiomyocyte regeneration, with a specific emphasis on the potential for targeting these mechanisms in adult cardiac models for repair after injury.

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“…Zebrafish studies have revealed that hdac1 is involved in SHF heart development and adult cardiac regeneration (18,19). In zebrafish, hdac1 mutants have less cardiomyocytes (CMs) in the ventricle while inhibition of hdac1 (and other class I HDACs) reveal reduced proliferation during regenerative events (18,19,20,21). Zebrafish hdac1 mutants are embryonic lethal, similar to the mouse models, but MZsap130a mutants are viable as adults suggesting that hdac1 and sap130a may have distinct functions in zebrafish cardiogenesis (18,22).…”

Section: Introductionmentioning

confidence: 98%

“…HDACs have been reported to regulate many aspects of development, including cardiac development in zebrafish, mouse, and chick models, evidenced by treatment with a pan HDAC small molecule inhibitor, Trichostatin A (14,15,16,17). Zebrafish studies have revealed that hdac1 is involved in SHF heart development and adult cardiac regeneration (18,19). In zebrafish, hdac1 mutants have less cardiomyocytes (CMs) in the ventricle while inhibition of hdac1 (and other class I HDACs) reveal reduced proliferation during regenerative events (18,19,20,21).…”

Section: Introductionmentioning

confidence: 99%

Sin3a Associated Protein 130kDa, sap130, plays an evolutionary conserved role in zebrafish heart development

DeMoya

Forman-Rubinsky

Fontaine

et al. 2023

Preprint

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Hypoplastic left heart syndrome (HLHS) is a congenital heart disease where the left ventricle is reduced in size. A forward genetic screen in mice identified SIN3A associated protein 130kDa (Sap130), a protein in the chromatin modifying SIN3A/HDAC1 complex, as a gene contributing to the digenic etiology of HLHS. Here, we report the role of zebrafish sap130 genes in heart development. Loss of sap130a, one of two Sap130 orthologs, resulted in smaller ventricle size, a phenotype reminiscent to the hypoplastic left ventricle in mice. While cardiac progenitors were normal during somitogenesis, diminution of the ventricle size suggest the Second Heart Field (SHF) was the source of the defect. To explore the role of sap130a in gene regulation, transcriptome profiling was performed after the heart tube formation to identify candidate pathways and genes responsible for the small ventricle phenotype. Genes involved in cardiac differentiation and cell communication were dysregulated in sap130a, but not in sap130b mutants. Confocal light sheet analysis measured deficits in cardiac output in MZsap130a supporting the notion that cardiomyocyte maturation was disrupted. Lineage tracing experiments revealed a significant reduction of SHF cells in the ventricle that resulted in increased outflow tract size. These data suggest that sap130a is involved in cardiogenesis via regulating the accretion of SHF cells to the growing ventricle and in their subsequent maturation for cardiac function. Further, genetic studies revealed an interaction between hdac1 and sap130a, in the incidence of small ventricles. These studies highlight the conserved role of Sap130a and Hdac1 in zebrafish cardiogenesis.

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Histone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish

Cited by 7 publications

References 46 publications

Cardiac Acetylation in Metabolic Diseases

Cardiac Acetylation in Metabolic Diseases

Targeting Epigenetic Regulation of Cardiomyocytes through Development for Therapeutic Cardiac Regeneration after Heart Failure

Sin3a Associated Protein 130kDa, sap130, plays an evolutionary conserved role in zebrafish heart development

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