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Coordinating Regulation of Gene Expression in Cardiovascular Disease: Interactions between Chromatin Modifiers and
Ashley J Bauer1,2, Kathleen A Martin1,2
1Department of Medicine (Cardiovascular Medicine), Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT, USA.
Insights
Epigenetic modifiers and transcription factors interact to regulate gene expression in cardiovascular disease (CVD). Understanding these complex interactions is crucial for developing novel CVD therapeutics.
Area of Science:
- Cardiovascular Biology
- Epigenetics
- Molecular Biology
Background:
- Cardiovascular disease (CVD) is a major cause of mortality and economic burden.
- CVD pathogenesis involves complex genetic and environmental risk factors leading to dysregulated gene expression.
- Epigenetics, through chromatin structure and accessibility, plays a significant role in gene expression regulation.
Purpose of the Study:
- To review the interaction between epigenetic modifiers and transcription factors in cardiovascular disease.
- To highlight the emerging understanding of how these processes coordinately regulate gene expression.
- To identify challenges and future directions in studying these interactions.
Main Methods:
- Literature review focusing on epigenetic and transcriptional regulation in CVD.
- Synthesis of current knowledge on chromatin modifiers, DNA methylation, histone modifications, and transcription factors.
- Discussion of technical challenges and potential advancements in the field.
Main Results:
- Epigenetic modifiers influence gene expression by altering DNA, histones, and transcription factor recruitment.
- The interplay between epigenetic and transcriptional control is critical but not fully understood.
- Current research often focuses on either epigenetic or transcriptional control separately.
Conclusions:
- Understanding the integration of epigenetic and transcriptional regulation is essential for advancing CVD basic mechanisms.
- Novel therapeutic strategies for CVD can be developed by studying these interactions.
- Improved technical approaches are needed to fully elucidate the temporal and spatial relationships involved.
Abstract:
Cardiovascular disease is a leading cause of death with increasing economic burden. The pathogenesis of cardiovascular diseases is complex, but can arise from genetic and/or environmental risk factors. This can lead to dysregulated gene expression in numerous cell types including cardiomyocytes, endothelial cells, vascular smooth muscle cells, and inflammatory cells. While initial studies addressed transcriptional control of gene expression, epigenetics has been increasingly appreciated to also play an important role in this process through alterations in chromatin structure and gene accessibility. Chromatin-modifying proteins including enzymes that modulate DNA methylation, histone methylation, and histone acetylation can influence gene expression in numerous ways. These chromatin modifiers and their marks can promote or prevent transcription factor recruitment to regulatory regions of genes through modifications to DNA, histones, or the transcription factors themselves. This review will focus on the emerging question of how epigenetic modifiers and transcription factors interact to coordinately regulate gene expression in cardiovascular disease. While most studies have addressed the roles of either epigenetic or transcriptional control, our understanding of the integration of these processes is only just beginning. Interrogating these interactions is challenging, and improved technical approaches will be needed to fully dissect the temporal and spatial relationships between transcription factors, chromatin modifiers, and gene expression in cardiovascular disease. We summarize the current state of the field and provide perspectives on limitations and future directions. Through studies of epigenetic and transcriptional interactions, we can advance our understanding of the basic mechanisms of cardiovascular disease pathogenesis to develop novel therapeutics.