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

doi:10.1016/j.isci.2020.101728

Exposure to Air Pollution Disrupts Circadian Rhythm through Alterations in Chromatin Dynamics

iScience. 2020 Oct 24;23(11):101728. doi: 10.1016/j.isci.2020.101728. eCollection 2020 Nov 20.

Authors

Rengasamy Palanivel¹, Vinesh Vinayachandran¹, Shyam Biswal², Jeffrey A Deiuliis¹, Roshan Padmanabhan³, Bongsoo Park², Roopesh Singh Gangwar¹, Jared C Durieux⁴, Elaine Ann Ebreo Cara¹, Lopa Das¹, Graham Bevan¹, Zahi A Fayad⁵, Ahmed Tawakol⁶, Mukesh K Jain^{1

4}, Sujata Rao^{7

8}, Sanjay Rajagopalan^{1

4}

Affiliations

¹ Cardiovascular Research Institute, Department of Medicine, University Hospitals/Case Western Reserve University, Cleveland, OH, USA.
² Department of Environmental Health and Engineering, Johns Hopkins University, Baltimore, MD, USA.
³ Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
⁴ Harrington Heart and Vascular Institute, University Hospital Cleveland Medical Center, Cleveland, OH, USA.
⁵ BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁶ Cardiology Division and Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
⁸ Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA.

Abstract

Particulate matter ≤2.5μm (PM_2.5) 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 PM_2.5 alone, or with light at night exposure (LL) on metabolism. PM_2.5 induced peripheral insulin resistance, circadian rhythm (CR) dysfunction, and metabolic and brown adipose tissue (BAT) dysfunction, akin to LL (with no additive interaction between PM_2.5 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 PM_2.5 by ATAC-seq. The histone deacetylases 2, 3, and 4 were downregulated with PM_2.5 exposure, with increased promoter occupancy by the histone acetyltransferase p300 as evidenced by ChIP-seq. These findings suggest a previously unrecognized role of PM_2.5 in promoting CR disruption and metabolic dysfunction through epigenetic regulation of circadian targets.

Keywords: Environmental Health; Metabolic Engineering; Pollution; Transcriptomics.