Stress and the epigenetic landscape: a link to the pathobiology of human diseases? - PubMed (original) (raw)

Review

. 2010 Nov;11(11):806-12.

doi: 10.1038/nrg2881. Epub 2010 Oct 5.

Affiliations

Review

Sarah E Johnstone et al. Nat Rev Genet. 2010 Nov.

Abstract

Accumulating evidence points to a major role for chronic stress of cell renewal systems in the pathogenesis of important human diseases, including cancer, atherosclerosis and diabetes. Here we discuss emerging evidence that epigenetic abnormalities may make substantial contributions to these stress-induced pathologies. Although the mechanisms remain to be fully elucidated, we suggest that chronic stress can elicit heritable changes in the chromatin landscape that 'lock' cells in abnormal states, which then lead to disease. We emphasize the need to investigate epigenetic states in disease and links to stress and to consider how the knowledge gained through these studies may foster new means of disease prevention and management.

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Figures

Figure 1

Figure 1. The effect of stress on cell renewal systems

a | In an acute stress setting, transient stress might spare tissue stem cells but injure other cell types. This could lead to transient mobilization of progenitor cells (beige) to replenish differentiated cells (red and orange) and achieve tissue homeostasis. b | In a chronic stress setting, there is a more pronounced and ongoing effect on cell renewal systems with injury of all cell types, including stem cells (yellow). The tissue response involves mobilization and continued renewal of both stem cells and progenitor cells. Genetic and epigenetic changes can lead to altered states of these cells with resultant abnormal tissue homeostasis and predisposition to diseases such as cancer.

Figure 2

Figure 2. Perturbations caused by chronic stress

Chronic stress may result in epigenetic changes. For example, alterations in DNA methylation, histone modifications and nucleosome positioning might occur. In the example shown, the changes result in gene silencing. The epigenetic changes may result in heritable patterns of altered gene expression that result in abnormal cell states: proliferation, dysfunction or loss, or a change of state. Such changes can contribute to disease, as discussed in the text. The histone modifications shown here associated with active transcription are histone H3 lysine 4 dimethylation (H3K4me2) and H3 lysine 9 acetylation (H3K9ac); the modifications associated with transcriptional repression are H3 lysine 27 trimethylation (H3K27me3) and H3 lysine 9 trimethylation (H3K9me3).

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