Environmental Epigenetics of Diesel Particulate Matter Toxicogenomics
1
Department of Pediatrics & Human Development, Michigan State University, Grand Rapids, MI 49503, USA
2
Center for Research in Autism, Intellectual, and other Neurodevelopmental Disabilities, Michigan State University, East Lansing, MI 48824, USA
3
Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA
4
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2020, 17(20), 7386; https://doi.org/10.3390/ijerph17207386
Received: 28 August 2020 / Revised: 7 October 2020 / Accepted: 8 October 2020 / Published: 10 October 2020
(This article belongs to the Special Issue Environmental Epigenetics: Implications for Health and Disease)
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by disruptions in social communication and behavioral flexibility. Both genetic and environmental factors contribute to ASD risk. Epidemiologic studies indicate that roadway vehicle exhaust and in utero exposure to diesel particulate matter (DPM) are associated with ASD. Using the Comparative Toxicogenomics Database (CTD), we identified genes connected to DPM exposure and ASD, extracted the known enhancers/promoters of the identified genes, and integrated this with Assay for Transposase Accessible Chromatin (ATAC-seq) data from DPM-exposed human neural progenitor cells. Enhancer/promoter elements with significantly different chromosome accessibility revealed enriched DNA sequence motifs with transcription factor binding sites for EGR1. Variant extraction for linkage disequilibrium blocks of these regions followed by analysis through Genome Wide Association Studies (GWAS) revealed multiple neurological trait associations including exploratory eye movement and brain volume measurement. This approach highlights the effects of pollution on the regulatory regions of genes implicated in ASD by genetic studies, indicating convergence of genetic and environmental factors on molecular networks that contribute to ASD. Integration of publicly available data from the CTD, cell culture exposure studies, and phenotypic genetics synergize extensive evidence of chemical exposures on gene regulation for altered brain development.
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MDPI and ACS Style
Bilinovich, S.M.; Lewis, K.; Thompson, B.L.; Prokop, J.W.; Campbell, D.B. Environmental Epigenetics of Diesel Particulate Matter Toxicogenomics. Int. J. Environ. Res. Public Health 2020, 17, 7386.
AMA Style
Bilinovich SM, Lewis K, Thompson BL, Prokop JW, Campbell DB. Environmental Epigenetics of Diesel Particulate Matter Toxicogenomics. International Journal of Environmental Research and Public Health. 2020; 17(20):7386.
Chicago/Turabian StyleBilinovich, Stephanie M.; Lewis, Kristy; Thompson, Barbara L.; Prokop, Jeremy W.; Campbell, Daniel B. 2020. "Environmental Epigenetics of Diesel Particulate Matter Toxicogenomics" Int. J. Environ. Res. Public Health 17, no. 20: 7386.
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