Abstract
The epigenome refers to the complete set of heritable chemical modifications made to DNA and histone proteins. Certainly, the most well characterized epigenetic mark is the covalent addition of a methyl group to a CpG dinucleotide site in the genome. The DNA methylome—a collection of methyl marks established during embryogenesis—creates a complex regulatory network involved in cell type differentiation, homeostasis and regulating gene expression in response to environmental stimuli and stress throughout life. Collectively, an increasing body of research supports the notion that over time, diverging methylomes may account for substantial phenotypic discordance in monozygotic-twins and explain disparate susceptibilities to age-related disease. We review this evidence and discuss how a greater insight into the mechanisms of age-related epigenetic dysregulation may inform strategies for molecular diagnostics and therapeutic intervention.
Highlights
The term epigenetics first arose to describe heritable changes in gene expression that did not involve changes to the base pair coding sequence of DNA, and to explain, in part, how cells with an identical genetic make-up can give rise to completely different tissue types [1]
CpG sites are often not in isolation: rather, they are embedded in the genome as discrete clusters of CpG sites that range in size from 0.5 to 2 kilobases and are frequently located in the 5’ adjacent regions of transcriptional start sites [3]
Stochastic differential methylation patterns that arise in aging individuals create an epigenetic mosaicism that may allow for the selection of biological defects leading to cancer and other age-related diseases (Figure 2B) [2,55,66,125]
Summary
The term epigenetics first arose to describe heritable changes in gene expression that did not involve changes to the base pair coding sequence of DNA, and to explain, in part, how cells with an identical genetic make-up can give rise to completely different tissue types [1]. In combination with covalent modifications to histone (chromatin proteins) tails, somatic heritability of DNA methylation marks established during development leads to the persistence of highly tissue and cell type specific patterns of methylation [4,17,18,19].
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