TY - JOUR
T1 - Exposure to Air Pollution Disrupts Circadian Rhythm through Alterations in Chromatin Dynamics
AU - Palanivel, Rengasamy
AU - Vinayachandran, Vinesh
AU - Biswal, Shyam
AU - Deiuliis, Jeffrey A.
AU - Padmanabhan, Roshan
AU - Park, Bongsoo
AU - Gangwar, Roopesh Singh
AU - Durieux, Jared C.
AU - Ebreo Cara, Elaine Ann
AU - Das, Lopa
AU - Bevan, Graham
AU - Fayad, Zahi A.
AU - Tawakol, Ahmed
AU - Jain, Mukesh K.
AU - Rao, Sujata
AU - Rajagopalan, Sanjay
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/11/20
Y1 - 2020/11/20
N2 - 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.
AB - 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.
KW - Environmental Health
KW - Metabolic Engineering
KW - Pollution
KW - Transcriptomics
UR - http://www.scopus.com/inward/record.url?scp=85097436762&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2020.101728
DO - 10.1016/j.isci.2020.101728
M3 - Article
AN - SCOPUS:85097436762
SN - 2589-0042
VL - 23
JO - iScience
JF - iScience
IS - 11
M1 - 101728
ER -