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Review
. 2011 May;26(3):209-15.
doi: 10.1097/HCO.0b013e328345986e.

Epigenetics in cardiovascular disease

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Review

Epigenetics in cardiovascular disease

Apurva V Shirodkar et al. Curr Opin Cardiol. 2011 May.

Abstract

Purpose of review: To provide an overview of the biological processes implicated in chromatin-based pathways that control endothelial gene expression patterns in both health and disease and highlight how these processes are relevant to cardiovascular disease.

Recent findings: Epigenetics refers to chromatin-based pathways important in the regulation of gene expression and includes three distinct, but highly interrelated, mechanisms: DNA methylation, histone density and posttranslational modifications, and RNA-based mechanisms. It is of great interest that epigenetic regulation of genes enriched in the vascular endothelium is a prominent regulatory pathway. How environmental cues within the vasculature, such as hemodynamic forces or hypoxia, influence these epigenetic mechanisms will be reviewed.

Summary: Although a newer area for study, exciting new evidence identifies that epigenetic processes are highly dynamic and respond to a myriad of environmental stimuli. Integrating chromatin-based pathways into our understanding of gene expression offers newer insight into disease processes.

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Figures

Figure 1
Figure 1. Chromatin-based mechanisms can regulate gene expression profiles
Epigenetics encompasses three nuclear processes: (1) DNA methylation, (2) histone density and posttranslational modifications, and (3) RNA-based mechanisms. DNA methylation occurs symmetrically at CpG dinucleotides, and is responsible for gene silencing. Recently described hydroxymethyla-tion is also present on DNA. Histone density can affect the accessibility of the chromatin to chromatin remodelers and transcription factors. Posttranslational modifications on N-terminal tails of histone proteins can modulate the interactions of histone proteins with DNA. RNA-based mechanisms include the production of long noncoding RNA (lncRNA), which can interact with chromatin and chromatin-modifying complexes to regulate gene expression. Adapted with permission from [5].
Figure 2
Figure 2. Signature chromatin domains at active and inactive gene promoters
Specific chromatin marks have been characterized at active (a) and inactive (b) genes, where the arrow denotes the start of transcription. (a) Generally, activated promoters are characterized by an absence of promoter DNA methylation (CpG sites shown as black lines), an enrichment of hyperacetylated histones H3 and H4, H3K4me3 at the promoter and H3K36me3 along the transcribed region. Transcribed regions do not demonstrate H3K27me3 marks. (b) Inactive promoters are generally characterized by dense DNA methylation (shown as filled circles at CG sites), increased histone density, and enrichment of H3K27me3 and/or H3K9me3 marks.

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