Genome-wide DNA methylation sequencing identifies epigenetic perturbations in the upper airways under long-term exposure to moderate levels of ambient air pollution

• Verfasst von: Messingschlager, Marey [VerfasserIn]
• Verfasst von: Bartel-Steinbach, Martina [VerfasserIn]
• Verfasst von: Mackowiak, Sebastian D. [VerfasserIn]
• Verfasst von: Denkena, Johanna [VerfasserIn]
• Verfasst von: Bieg, Matthias [VerfasserIn]
• Verfasst von: Klös, Matthias [VerfasserIn]
• Verfasst von: Seegebarth, Anke [VerfasserIn]
• Verfasst von: Straff, Wolfgang [VerfasserIn]
• Verfasst von: Süring, Katrin [VerfasserIn]
• Verfasst von: Ishaque, Naveed [VerfasserIn]
• Verfasst von: Eils, Roland [VerfasserIn]
• Verfasst von: Lehmann, Irina [VerfasserIn]
• Verfasst von: Lermen, Dominik [VerfasserIn]
• Verfasst von: Trump, Saskia [VerfasserIn]
• Titel: Genome-wide DNA methylation sequencing identifies epigenetic perturbations in the upper airways under long-term exposure to moderate levels of ambient air pollution
• Verf.angabe: Marey Messingschlager, Martina Bartel-Steinbach, Sebastian D. Mackowiak, Johanna Denkena, Matthias Bieg, Matthias Klös, Anke Seegebarth, Wolfgang Straff, Katrin Süring, Naveed Ishaque, Roland Eils, Irina Lehmann, Dominik Lermen, Saskia Trump
• E-Jahr: 2023
• Jahr: 15 September 2023
• Umfang: 14 S.
• Fussnoten: Online verfügbar: 20. Juni 2023, Artikelversion: 28. Juni 2023 ; Gesehen am 22.08.2023
• Titel Quelle: Enthalten in: Environmental research
• Ort Quelle: San Diego, Calif. : Elsevier, 1967
• Jahr Quelle: 2023
• Band/Heft Quelle: 233(2023) vom: Sept., Artikel-ID 116413, Seite 1-14
• ISSN Quelle: 1096-0953
• DOI: doi:10.1016/j.envres.2023.116413
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Ambient air pollution
• Sach-SW: DNA methylation
• Sach-SW: Nasal lavage
• Sach-SW: NEBNext enzymatic methyl-seq
• Sach-SW: PM
• Sach-SW: Whole-genome methylome sequencing
• K10plus-PPN: 185723331X

Abstract

While the link between exposure to high levels of ambient particulate matter (PM) and increased incidences of respiratory and cardiovascular diseases is widely recognized, recent epidemiological studies have shown that low PM concentrations are equally associated with adverse health effects. As DNA methylation is one of the main mechanisms by which cells regulate and stabilize gene expression, changes in the methylome could constitute early indicators of dysregulated signaling pathways. So far, little is known about PM-associated DNA methylation changes in the upper airways, the first point of contact between airborne pollutants and the human body. Here, we focused on cells of the upper respiratory tract and assessed their genome-wide DNA methylation pattern to explore exposure-associated early regulatory changes. Using a mobile epidemiological laboratory, nasal lavage samples were collected from a cohort of 60 adults that lived in districts with records of low (Simmerath) or moderate (Stuttgart) PM10 levels in Germany. PM10 concentrations were verified by particle measurements on the days of the sample collection and genome-wide DNA methylation was determined by enzymatic methyl sequencing at single-base resolution. We identified 231 differentially methylated regions (DMRs) between moderately and lowly PM10 exposed individuals. A high proportion of DMRs overlapped with regulatory elements, and DMR target genes were involved in pathways regulating cellular redox homeostasis and immune response. In addition, we found distinct changes in DNA methylation of the HOXA gene cluster whose methylation levels have previously been linked to air pollution exposure but also to carcinogenesis in several instances. The findings of this study suggest that regulatory changes in upper airway cells occur at PM10 levels below current European thresholds, some of which may be involved in the development of air pollution-related diseases.