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 - Funding Information:
We are grateful to Dr. Chris A. Flask, Associate Professor, Department of Radiology, School of Medicine for determining body fat/water composition (MRI) and for conducting the FDG uptake (PET/CT) study and analysis. We thank Dr. Colleen Croniger, Associate Professor, Department of Nutrition School of Medicine for mice metabolic cage study and analysis. We thank Dr. Brendan Eck, Department of Biomedical Engineering for making 3D images for FDG uptake. We acknowledge Jenifer Mikulan, Institute Pathology for BAT histopathological study. We thank Dr. E Ricky Chan, Institute of Computational Biology, Case Western Reserve University for transcriptome and ATAC-seq analysis. This work was supported by the National Institute of Environmental Health Sciences (NIEHS) of the National Institutes of Health (NIH) under Award Numbers U01ES026721 (to S.B. and S.R.) and 5R01ES019616 and 1RO1ES015146 (to S.R.)
Funding Information:
We are grateful to Dr. Chris A. Flask, Associate Professor, Department of Radiology, School of Medicine for determining body fat/water composition (MRI) and for conducting the FDG uptake (PET/CT) study and analysis. We thank Dr. Colleen Croniger, Associate Professor, Department of Nutrition School of Medicine for mice metabolic cage study and analysis. We thank Dr. Brendan Eck, Department of Biomedical Engineering for making 3D images for FDG uptake. We acknowledge Jenifer Mikulan, Institute Pathology for BAT histopathological study. We thank Dr. E Ricky Chan, Institute of Computational Biology, Case Western Reserve University for transcriptome and ATAC-seq analysis. This work was supported by the National Institute of Environmental Health Sciences (NIEHS) of the National Institutes of Health (NIH) under Award Numbers U01ES026721 (to S.B. and S.R.) and 5R01ES019616 and 1RO1ES015146 (to S.R.), S.Rajagopalan and S.B. conceptualized and initiated PM2.5-based exposure design, edited and approved, wrote, and finalized the final manuscript. J.A.D. designed the light at night exposure experiments, edited the manuscript. R.P. and V.V. performed most experiments. E.A.E.C. conducted the circadian gene expression study. R. Padmanabhan and B.P. conducted bioinformatics analysis. R.P. E.A.E.C. R.S.G. L.D. and G.B. conducted PM exposure and tissue collection. R.P. conducted phenotype assays including BAT histology, microscope imaging, and GTT/ITT. V.V. prepared sequencing libraries and performed OMNI ATAC-seq. J.C.D. performed statistical analysis for all experiments. R.P. V.V. and S.R. wrote a draft manuscript. S. Rajagopalan, S. Rao, M.J.K. Z.F. and A.T. contributed to revising and finalizing the manuscript. The authors declare no competing financial interests.
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
UR - http://www.scopus.com/inward/citedby.url?scp=85097436762&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2020.101728
DO - 10.1016/j.isci.2020.101728
M3 - Article
C2 - 33241196
AN - SCOPUS:85097436762
VL - 23
JO - iScience
JF - iScience
SN - 2589-0042
IS - 11
M1 - 101728
ER -