Environmental Epigenetics of Diesel Particulate Matter Toxicogenomics.

Area of Science:

• Environmental toxicology
• Neurodevelopmental disorders
• Genomics and epigenetics

Background:

• Autism spectrum disorder (ASD) is a neurodevelopmental condition influenced by genetic and environmental factors.
• Epidemiological studies suggest a link between prenatal exposure to roadway vehicle exhaust, including diesel particulate matter (DPM), and increased ASD risk.

Purpose of the Study:

• To investigate the molecular mechanisms connecting DPM exposure to ASD risk.
• To identify how environmental pollutants affect gene regulatory elements in neural cells relevant to ASD.

Main Methods:

• Utilized the Comparative Toxicogenomics Database (CTD) to identify genes associated with DPM exposure and ASD.
• Integrated gene regulatory information (enhancers/promoters) with ATAC-seq data from DPM-exposed human neural progenitor cells.
• Analyzed DNA sequence motifs, transcription factor binding sites (EGR1), and performed Genome Wide Association Studies (GWAS) on linked genetic variants.

Main Results:

• Identified specific enhancer/promoter regions with altered chromatin accessibility upon DPM exposure.
• Discovered enriched DNA motifs and transcription factor binding sites (EGR1) in these regulatory regions.
• GWAS analysis of variants in these regions revealed associations with neurological traits like exploratory eye movement and brain volume.

Conclusions:

• Pollution exposure can affect the regulatory regions of genes implicated in ASD, highlighting the convergence of genetic and environmental factors.
• This research integrates diverse data sources to demonstrate how chemical exposures influence gene regulation and brain development in the context of ASD.