Exposure to environmental toxicants can lead to changes in normal epigenetic patterns and may be associated with the development of disease. For example, exposure to heavy metals, such as arsenic and nickel, is associated with epigenetic changes that may underlie the development of diseases known to be associated with these exposures, such as cancer, cardiovascular disease, neurological disorders, and autoimmune disease.
NIEHS-funded epigenetics research has made great strides in identifying methylation patterns or marks that result from a diverse array of exposures. However, epigenetic changes such as methylation only tell part of the story because they are essentially a biological readout of a far more complex regulatory process. Fully understanding the underlying mechanisms that contribute to disease requires a better understanding of how exposures affect and/or interact with the functional and regulatory elements that lead to changes in methylation patterns. To address this critical knowledge gap, NIEHS and the National Institute on Drug Abuse fund the multiphase Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription (TaRGET) program.
The first phase of the program, TaRGET I, is aimed at better defining the biology of how environmental exposures affect proteins and other elements involved in establishing and maintaining gene expression patterns and epigenetic modifications, such as DNA methylation. Researchers funded by this program are using model animals and cell studies to understand the mechanisms involved in the environmental control of gene regulation and the central role of epigenetics in the process by examining all interacting pathways involved in epigenetic modifications.
The second phase of this program, TaRGET II, has established a consortium consisting of five production awards and a Data Coordination Center to validate the robustness/feasibility of using surrogate tissues (e.g., peripheral blood lymphocytes) for detecting changes in epigenetic marks using mouse models. This phase is characterizing the epigenetic changes that are induced by environmental exposures in a variety of tissues and cell types (e.g., brain, lung, liver, skin, blood) and investigating factors, such as the timing of exposure and sex that influence whether induced changes are conserved across tissues. The TaRGET II Consortium will provide guidance on how to perform similar epigenomic analyses in human populations.
The third phase, TaRGET III, will support the expansion of data from population-based studies in which information on DNA methylation is being collected.
The fourth phase, TaRGET IV, will support integrated analyses in population-based studies, making use of a number of genomic and epigenomic databases to develop more comprehensive epigenomics/genomics analyses.