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

iScience (Nov 2020)

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

Journal volume & issue: Vol. 23, no. 11
p. 101728

Abstract

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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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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