title: Influence of environmental exposure on human epigenetic regulation.
abstract: Environmental toxicants can alter epigenetic regulatory features such as DNA methylation and microRNA expression. As the sensitivity of epigenomic regulatory features may be greatest during the in utero period, when critical windows are narrow, and when epigenomic profiles are being set, this review will highlight research focused on that period. I will focus on work in human populations, where the impact of environmental toxicants in utero, including cigarette smoke and toxic trace metals such as arsenic, mercury and manganese, on genome-wide, gene-specific DNA methylation has been assessed. In particular, arsenic is highlighted, as this metalloid has been the focus of a number of studies and its detoxification mechanisms are well understood. Importantly, the tissues and cells being examined must be considered in context in order to interpret the findings of these studies. For example, by studying the placenta, it is possible to identify potential epigenetic adaptations of key genes and pathways that may alter the developmental course in line with the developmental origins of health and disease paradigm. Alternatively, studies of newborn cord blood can be used to examine how environmental exposure in utero can impact the composition of cells within the peripheral blood, leading to immunological effects of exposure. The results suggest that in humans, like other vertebrates, there is a susceptibility for epigenomic alteration by the environment during intrauterine development, and this may represent a mechanism of plasticity of the organism in response to its environment as well as a mechanism through which long-term health consequences can be shaped.
authors.affiliation: Department of Pharmacology and Toxicology and Section of Epidemiology and Biostatistics in the Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA Carmen.j.marsit@dartmouth.edu.
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
mesh_terms: D004781:Environmental Exposure; D016021:Epidemiologic Studies; D044127:Epigenesis, Genetic; D006801:Humans; D012106:Research
keywords: DNA methylation; Environmental epidemiology; Epigenomics; Histone modification; miRNA