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

Rengasamy Palanivel, Vinesh Vinayachandran, Shyam Biswal, Jeffrey A. Deiuliis, Roshan Padmanabhan, Bongsoo Park, Roopesh Singh Gangwar, Jared C. Durieux, Elaine Ann Ebreo Cara, Lopa Das, Graham Bevan, Zahi A. Fayad, Ahmed Tawakol, Mukesh K. Jain, Sujata Rao, Sanjay Rajagopalan

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number101728
JournaliScience
Volume23
Issue number11
DOIs
StatePublished - Nov 20 2020

Keywords

  • Environmental Health
  • Metabolic Engineering
  • Pollution
  • Transcriptomics

ASJC Scopus subject areas

  • General

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