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
Affiliations
Rengasamy Palanivel
Cardiovascular Research Institute, Department of Medicine, University Hospitals/Case Western Reserve University, Cleveland, OH, USA
Vinesh Vinayachandran
Cardiovascular Research Institute, Department of Medicine, University Hospitals/Case Western Reserve University, Cleveland, OH, USA
Shyam Biswal
Department of Environmental Health and Engineering, Johns Hopkins University, Baltimore, MD, USA
Jeffrey A. Deiuliis
Cardiovascular Research Institute, Department of Medicine, University Hospitals/Case Western Reserve University, Cleveland, OH, USA
Roshan Padmanabhan
Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
Bongsoo Park
Department of Environmental Health and Engineering, Johns Hopkins University, Baltimore, MD, USA
Roopesh Singh Gangwar
Cardiovascular Research Institute, Department of Medicine, University Hospitals/Case Western Reserve University, Cleveland, OH, USA
Jared C. Durieux
Harrington Heart and Vascular Institute, University Hospital Cleveland Medical Center, Cleveland, OH, USA
Elaine Ann Ebreo Cara
Cardiovascular Research Institute, Department of Medicine, University Hospitals/Case Western Reserve University, Cleveland, OH, USA
Lopa Das
Cardiovascular Research Institute, Department of Medicine, University Hospitals/Case Western Reserve University, Cleveland, OH, USA
Graham Bevan
Cardiovascular Research Institute, Department of Medicine, University Hospitals/Case Western Reserve University, Cleveland, OH, USA
Zahi A. Fayad
BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Ahmed Tawakol
Cardiology Division and Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Mukesh K. Jain
Cardiovascular Research Institute, Department of Medicine, University Hospitals/Case Western Reserve University, Cleveland, OH, USA; Harrington Heart and Vascular Institute, University Hospital Cleveland Medical Center, Cleveland, OH, USA
Sujata Rao
Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA
Sanjay Rajagopalan
Cardiovascular Research Institute, Department of Medicine, University Hospitals/Case Western Reserve University, Cleveland, OH, USA; Harrington Heart and Vascular Institute, University Hospital Cleveland Medical Center, Cleveland, OH, USA; Corresponding author
Summary: 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.
