Environmental epigenetics: prospects for studying epigenetic mediation of exposure–response relationships

Abstract

Changes in epigenetic marks such as DNA methylation and histone acetylation are associated with a broad range of disease traits, including cancer, asthma, metabolic disorders, and various reproductive conditions. It seems plausible that changes in epigenetic state may be induced by environmental exposures such as malnutrition, tobacco smoke, air pollutants, metals, organic chemicals, other sources of oxidative stress, and the microbiome, particularly if the exposure occurs during key periods of development. Thus, epigenetic changes could represent an important pathway by which environmental factors influence disease risks, both within individuals and across generations. We discuss some of the challenges in studying epigenetic mediation of pathogenesis and describe some unique opportunities for exploring these phenomena.

Reprogramming of the human intestinal epigenome by surgical tissue transposition

“…This is partly because most human studies have been largely limited either to epidemiological approaches, where exposure time is often unknown, or in vitro systems, which, while useful, do not always recapitulate in vivo conditions (Wilson and Jones 1983;Christensen et al 2009;Cortessis et al 2012;Mill and Heijmans 2013;Zhu et al 2013). Our study using the human ileal neobladder is the first model that attempts to characterize and quantify the dynamic interaction between the local tissue environment and the epigenetics in vivo.…”

“…The role of the local tissue environment in maintaining normal DNA methylation patterns, and subsequently the cellular phenotype of differentiated human cells, however, has remained elusive as studies in human subjects have mostly been limited to in vitro models and/or epidemiological observations where the extent of environmental exposure is often not precisely known (Feil and Fraga 2011;Rakyan et al 2011;Cortessis et al 2012;Mill and Heijmans 2013).…”

DNA methylation and healthy human aging

“…A remarkable aspect of DNA methylation is that it can be modified by external factors, and in some cases, the resulting marks are heritable through cell divisions. This balance of responsiveness to stimuli and heritability results in a unique mechanism for lasting signatures of prior exposures that accumulate over the lifetime (Cortessis et al ., 2012; Feil & Fraga, 2012). As an example of a specific exposure that has been shown to leave a lasting signature, cigarette smoke has been linked to changes in DNA methylation at the AHRR locus both in smokers and in children of smokers (Saxonov et al ., 2006; Monick et al ., 2012; Joubert et al ., 2012; Shenker et al ., 2013; Sun et al ., 2013 Elliott et al ., 2014; Lee et al ., 2015; Shah et al ., 2014).…”

DNMT3a rs1550117 Polymorphism Association with Increased Risk of Helicobacter pylori Infection

“…Changes in epigenetic marks such as DNA methylation is associated with several diseases, including cancer, metabolic disorders, and various reproductive conditions (Cortessis et al, 2012). CpG island hypermethylation and genomic DNA hypomethylation are found in gastric tumors and premalignant lesions (Park et al, 2009), and H.pylori infection can induces aberrant CpG island hypermethylation in gastric mucosa (Nakajima et al, 2009;Park et al, 2009).…”