Toxicogenomic Insights into Environmental Toxicant Exposures: The TaRGET II Resource

Area of Science:

• Environmental epigenetics
• Toxicogenomics
• Molecular toxicology

Background:

• Environmental toxicants can disrupt gene expression and epigenetic regulation.
• These disruptions can lead to disease throughout an organism's life.
• Understanding the long-term molecular consequences of early-life exposures is crucial.

Purpose of the Study:

• To create a comprehensive resource detailing the epigenomic and transcriptomic effects of various toxicants.
• To investigate the persistence and specificity of these molecular changes.
• To provide accessible data for studying the link between environmental exposures and disease.

Main Methods:

• Longitudinal studies in mice exposed to specific toxicants (arsenic, lead, BPA, DEHP, TBT, TCDD, PM2.5).
• Generation of 2,570 epigenomes and 1,043 transcriptomes from multiple tissues at different life stages.
• Analysis of DNA methylation, chromatin accessibility, and gene expression patterns.

Main Results:

• Identified persistent, toxicant-specific, and sex-dependent changes in epigenomes and transcriptomes.
• Observed widespread gene expression disruption (14,908 genes), altered chromatin accessibility (87,409 elements), and DNA methylation changes (113,186 regions).
• Documented chromatin state switching in response to toxicant exposure.

Conclusions:

• Environmental exposures during early life can reprogram the epigenome and transcriptome in a lasting manner.
• The TaRGET II resource provides a high-resolution map of these molecular alterations.
• This publicly available data facilitates research into the pathogenesis of environmentally induced diseases.