Epigenetic Regulation of Cardiac Development, Regeneration and Disease

A special issue of Journal of Cardiovascular Development and Disease (ISSN 2308-3425). This special issue belongs to the section "Pediatric Cardiology and Congenital Heart Disease".

Deadline for manuscript submissions: closed (1 July 2023) | Viewed by 5697

Special Issue Editors


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Guest Editor
1. McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
2. Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Interests: cardiovascular development and regeneration; cardiomyopathy

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Guest Editor
Exposome, Epi/Genetics & Heart Development lab, Center for CardioVascular and Nutrition Research, Aix Marseille University, 13007 Marseille, France
Interests: congenital heart disease; heart development; cell fate decisions; gene regulation; epigenetic regulation; non-coding DNA; molecular biology; transgenic mouse models; pluripotent stem cells
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Special Issue Information

Dear Colleagues,

Congenital heart malformation is one of the leading causes of human birth defects, and cardiac diseases remain the major cause of adult morbidity and mortality both in developed countries and worldwide. Heart is the first organ to form during embryogenesis, and it functions to supply nutrient and oxygen to meet the metabolic demand of the body. After its initial formation at the ventral midline, the vertebrate heart undergoes a series of complex morphogenetic processes that transform the linear heart tube into a four-chambered pumping organ. Defects in these processes can manifest as a variety of congenital structural and/or physiological abnormalities that compromise cardiac function and affect the patient’s well-being. While increase in cardiac mass during development is primarily driven by the addition of differentiated cardiac progenitor cells into the developing heart and subsequent hyperplasia, postnatal cardiac growth in mammals is mainly achieved by hypertrophic growth of the cardiomyocytes, which withdraw from cell cycle and lose their ability to proliferate shortly after birth. The inability of the adult mammalian heart to regenerate and its reliance on reparative fibrotic response render the heart vulnerable to acute and chronic cardiac injuries, which likely contribute to the prevalence of acquired heart disease. Epigenetics refers to regulatory mechanisms that elicit heritable changes in gene expression and function without altering genomic DNA sequence. Epigenetic mechanisms, such as those involving DNA methylation and histone modifications, play fundamental roles in many biological processes. Epigenetic dysregulation can cause perturbed gene expression and thus lead to various congenital and acquired diseases. Given the importance of epigenetic regulation in biology and human disease, in this Special Issue of JCDD, we welcome submissions of original research and review articles as well as case reports with a focus on the epigenetic regulation of cardiac development, regeneration and disease.

Dr. Jiandong Liu
Dr. Sonia Stefanovic
Guest Editors

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Keywords

  • epigenetic regulation
  • cardiac development
  • cardiac morphogenesis
  • cardiac regeneration
  • congenital heart disease
  • acquired heart disease
  • chromatin regulation

Published Papers (3 papers)

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Research

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19 pages, 10151 KiB  
Article
H3K36 Di-Methylation Marks, Mediated by Ash1 in Complex with Caf1-55 and MRG15, Are Required during Drosophila Heart Development
by Jun-yi Zhu, Chen Liu, Xiaohu Huang, Joyce van de Leemput, Hangnoh Lee and Zhe Han
J. Cardiovasc. Dev. Dis. 2023, 10(7), 307; https://doi.org/10.3390/jcdd10070307 - 18 Jul 2023
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Abstract
Methyltransferases regulate transcriptome dynamics during development and aging, as well as in disease. Various methyltransferases have been linked to heart disease, through disrupted expression and activity, and genetic variants associated with congenital heart disease. However, in vivo functional data for many of the [...] Read more.
Methyltransferases regulate transcriptome dynamics during development and aging, as well as in disease. Various methyltransferases have been linked to heart disease, through disrupted expression and activity, and genetic variants associated with congenital heart disease. However, in vivo functional data for many of the methyltransferases in the context of the heart are limited. Here, we used the Drosophila model system to investigate different histone 3 lysine 36 (H3K36) methyltransferases for their role in heart development. The data show that Drosophila Ash1 is the functional homolog of human ASH1L in the heart. Both Ash1 and Set2 H3K36 methyltransferases are required for heart structure and function during development. Furthermore, Ash1-mediated H3K36 methylation (H3K36me2) is essential for healthy heart function, which depends on both Ash1-complex components, Caf1-55 and MRG15, together. These findings provide in vivo functional data for Ash1 and its complex, and Set2, in the context of H3K36 methylation in the heart, and support a role for their mammalian homologs, ASH1L with RBBP4 and MORF4L1, and SETD2, during heart development and disease. Full article
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17 pages, 13150 KiB  
Article
Rtf1 Transcriptionally Regulates Neonatal and Adult Cardiomyocyte Biology
by Adam D. Langenbacher, Fei Lu, Lauren Crisman, Zi Yi Stephanie Huang, Douglas J. Chapski, Thomas M. Vondriska, Yibin Wang, Chen Gao and Jau-Nian Chen
J. Cardiovasc. Dev. Dis. 2023, 10(5), 221; https://doi.org/10.3390/jcdd10050221 - 20 May 2023
Cited by 1 | Viewed by 2393
Abstract
The PAF1 complex component Rtf1 is an RNA Polymerase II-interacting transcription regulatory protein that promotes transcription elongation and the co-transcriptional monoubiquitination of histone 2B. Rtf1 plays an essential role in the specification of cardiac progenitors from the lateral plate mesoderm during early embryogenesis, [...] Read more.
The PAF1 complex component Rtf1 is an RNA Polymerase II-interacting transcription regulatory protein that promotes transcription elongation and the co-transcriptional monoubiquitination of histone 2B. Rtf1 plays an essential role in the specification of cardiac progenitors from the lateral plate mesoderm during early embryogenesis, but its requirement in mature cardiac cells is unknown. Here, we investigate the importance of Rtf1 in neonatal and adult cardiomyocytes using knockdown and knockout approaches. We demonstrate that loss of Rtf1 activity in neonatal cardiomyocytes disrupts cell morphology and results in a breakdown of sarcomeres. Similarly, Rtf1 ablation in mature cardiomyocytes of the adult mouse heart leads to myofibril disorganization, disrupted cell–cell junctions, fibrosis, and systolic dysfunction. Rtf1 knockout hearts eventually fail and exhibit structural and gene expression defects resembling dilated cardiomyopathy. Intriguingly, we observed that loss of Rtf1 activity causes a rapid change in the expression of key cardiac structural and functional genes in both neonatal and adult cardiomyocytes, suggesting that Rtf1 is continuously required to support expression of the cardiac gene program. Full article
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Review

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17 pages, 1475 KiB  
Review
The Roles of Histone Lysine Methyltransferases in Heart Development and Disease
by Jun-yi Zhu, Joyce van de Leemput and Zhe Han
J. Cardiovasc. Dev. Dis. 2023, 10(7), 305; https://doi.org/10.3390/jcdd10070305 - 18 Jul 2023
Cited by 2 | Viewed by 1650
Abstract
Epigenetic marks regulate the transcriptomic landscape by facilitating the structural packing and unwinding of the genome, which is tightly folded inside the nucleus. Lysine-specific histone methylation is one such mark. It plays crucial roles during development, including in cell fate decisions, in tissue [...] Read more.
Epigenetic marks regulate the transcriptomic landscape by facilitating the structural packing and unwinding of the genome, which is tightly folded inside the nucleus. Lysine-specific histone methylation is one such mark. It plays crucial roles during development, including in cell fate decisions, in tissue patterning, and in regulating cellular metabolic processes. It has also been associated with varying human developmental disorders. Heart disease has been linked to deregulated histone lysine methylation, and lysine-specific methyltransferases (KMTs) are overrepresented, i.e., more numerous than expected by chance, among the genes with variants associated with congenital heart disease. This review outlines the available evidence to support a role for individual KMTs in heart development and/or disease, including genetic associations in patients and supporting cell culture and animal model studies. It concludes with new advances in the field and new opportunities for treatment. Full article
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