Epigenetic changes modify the way genetic information is expressed without directly changing the genetic code stored in DNA. Exposure to toxic environmental substances 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 cancer, cardiovascular and autoimmune diseases, and neurological disorders.

NIEHS-funded epigenetics research has made strides in identifying methylation patterns and other modifications associated with an array of exposures. However, research is lacking on the molecular mechanisms that drive those methylation changes. To address this knowledge gap, NIEHS and the National Institute on Drug Abuse funded the first phase of the multiphase Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription (TaRGET) program.

The first phase, TaRGET I, focuses on how environmental exposures affect proteins and other biological factors involved in establishing and maintaining gene expression patterns and epigenetic modifications, such as DNA methylation. Researchers funded by this program pursued studies in animals and cells to examine interacting molecular pathways involved in epigenetic modifications and how they relate to gene regulation.

The second phase of this program, TaRGET II, established a consortium consisting of five production awards and a Data Coordination Center to validate the possibility of using surrogate tissues — accessible tissues that stand in for harder-to-reach tissues — from mice for detecting epigenetic changes.

This phase is characterizing epigenetic changes 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 of the organism — that influence whether those changes are conserved across tissues. The TARGET II Consortium has informed similar epigenomic analyses in human populations.