Exposure to Air Pollution Disrupts Circadian Rhythm through Alterations in Chromatin Dynamics

• Published in: iScience Vol. 23; no. 11; p. 101728
• Main Authors: Palanivel, Rengasamy, Vinayachandran, Vinesh, Biswal, Shyam, Deiuliis, Jeffrey A., Padmanabhan, Roshan, Park, Bongsoo, Gangwar, Roopesh Singh, Durieux, Jared C., Ebreo Cara, Elaine Ann, Das, Lopa, Bevan, Graham, Fayad, Zahi A., Tawakol, Ahmed, Jain, Mukesh K., Rao, Sujata, Rajagopalan, Sanjay
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20-11-2020; Elsevier
• Subjects: Environmental Health; Metabolic Engineering; Pollution; Transcriptomics; Metabolic Engineering; Pollution; Environmental Health; Transcriptomics
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2020.101728

Particulate matter ≤2.5μm (PM2.5) air pollution is a leading environmental risk factor contributing disproportionately to the global burden of non-communicable disease. We compared impact of chronic exposure to PM2.5 alone, or with light at night exposure (LL) on metabolism. PM2.5 induced peripheral insulin resistance, circadian rhythm (CR) dysfunction, and metabolic and brown adipose tissue (BAT) dysfunction, akin to LL (with no additive interaction between PM2.5 and LL). Transcriptomic analysis of liver and BAT revealed widespread but unique alterations in CR genes, with evidence for differentially accessible promoters and enhancers of CR genes in response to PM2.5 by ATAC-seq. The histone deacetylases 2, 3, and 4 were downregulated with PM2.5 exposure, with increased promoter occupancy by the histone acetyltransferase p300 as evidenced by ChIP-seq. These findings suggest a previously unrecognized role of PM2.5 in promoting CR disruption and metabolic dysfunction through epigenetic regulation of circadian targets.
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•Air pollution disrupts the circadian rhythm (CR) similar to light at night•Dysregulated circadian genes result in insulin resistance and metabolic diseases•PM2.5 alters chromatin structure of circadian genes at regulatory regions•PM2.5 alters chromatin structure by recruiting histone acetyl transferase (HAT), p300
Environmental Health; Pollution; Transcriptomics; Metabolic Engineering