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Updated: Apr 20, 2026
Epigenetic Regulation of Cardiac Differentiation of Embryonic Stem Cells and Tissues
Published on: June 3, 2016
Epigenetic regulation of cardiac myocyte differentiation
Kyohei Oyama1, Danny El-Nachef1, Yiqiang Zhang1
1Division of Cardiology, Department of Medicine, Center for Cardiovascular Biology and Institute for Stem Cell and Regenerative Medicine, University of Washington Seattle, WA, USA.
Abstract:
Cardiac myocytes (CMs) proliferate robustly during fetal life but withdraw permanently from the cell cycle soon after birth and undergo terminal differentiation. This cell cycle exit is associated with the upregulation of a host of adult cardiac-specific genes. The vast majority of adult CMs (ACMs) do not reenter cell cycle even if subjected to mitogenic stimuli. The basis for this irreversible cell cycle exit is related to the stable silencing of cell cycle genes specifically involved in the progression of G2/M transition and cytokinesis. Studies have begun to clarify the molecular basis for this stable gene repression and have identified epigenetic and chromatin structural changes in this process. In this review, we summarize the current understanding of epigenetic regulation of CM cell cycle and cardiac-specific gene expression with a focus on histone modifications and the role of retinoblastoma family members.
Insights
Cardiac myocytes (CMs) permanently exit the cell cycle after birth, upregulating adult cardiac genes. This review explores the epigenetic mechanisms, including histone modifications, that stably silence cell cycle genes in adult CMs.
Area of Science:
- Cardiovascular Biology
- Epigenetics
- Cell Cycle Regulation
Background:
- Cardiac myocytes (CMs) exhibit robust proliferation during fetal development but permanently withdraw from the cell cycle postnatally.
- This cell cycle exit is crucial for terminal differentiation and the expression of adult cardiac-specific genes.
- Adult CMs (ACMs) resist re-entry into the cell cycle, even with mitogenic stimulation, due to stable gene silencing.
Purpose of the Study:
- To review the current understanding of epigenetic regulation governing CM cell cycle.
- To elucidate the mechanisms controlling cardiac-specific gene expression in ACMs.
- To highlight the roles of histone modifications and retinoblastoma family members in these processes.
Main Methods:
- This review synthesizes findings from existing studies on CM cell cycle control.
- Focuses on epigenetic mechanisms, including histone modifications and chromatin structure.
- Examines the involvement of retinoblastoma family proteins.
Main Results:
- Permanent cell cycle exit in ACMs is linked to stable silencing of genes essential for G2/M transition and cytokinesis.
- Epigenetic modifications and chromatin structural changes underpin this stable gene repression.
- Retinoblastoma family members play a significant role in regulating gene expression and cell cycle arrest.
Conclusions:
- Epigenetic regulation, particularly histone modifications, is critical for maintaining the quiescent state of ACMs.
- Understanding these mechanisms is key to potentially reactivating CM proliferation for cardiac repair.
- The review consolidates knowledge on the molecular basis of irreversible cell cycle exit in cardiac myocytes.
