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  • 标题:Exposure to Air Pollution Disrupts Circadian Rhythm through Alterations in Chromatin Dynamics
  • 本地全文:下载
  • 作者:Rengasamy Palanivel ; Vinesh Vinayachandran ; Shyam Biswal
  • 期刊名称:iScience
  • 印刷版ISSN:2589-0042
  • 出版年度:2020
  • 卷号:23
  • 期号:11
  • 页码:1-35
  • DOI:10.1016/j.isci.2020.101728
  • 语种:English
  • 出版社:Elsevier
  • 摘要:SummaryParticulate 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 PM2.5alone, or with light at night exposure (LL) on metabolism. PM2.5induced peripheral insulin resistance, circadian rhythm (CR) dysfunction, and metabolic and brown adipose tissue (BAT) dysfunction, akin to LL (with no additive interaction between PM2.5and 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 PM2.5by ATAC-seq. The histone deacetylases 2, 3, and 4 were downregulated with PM2.5exposure, with increased promoter occupancy by the histone acetyltransferase p300 as evidenced by ChIP-seq. These findings suggest a previously unrecognized role of PM2.5in promoting CR disruption and metabolic dysfunction through epigenetic regulation of circadian targets.Graphical AbstractDisplay OmittedHighlights•Air pollution disrupts the circadian rhythm (CR) similar to light at night•Dysregulated circadian genes result in insulin resistance and metabolic diseases•PM2.5alters chromatin structure of circadian genes at regulatory regions•PM2.5alters chromatin structure by recruiting histone acetyl transferase (HAT), p300Environmental Health; Pollution; Transcriptomics; Metabolic Engineering
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