Disease relevant modifications of the methylome and transcriptome by particulate matter (PM2.5) from biomass combustion

Abstract: Exposure to particulate matter (PM) is recognized as a major health hazard, but molecular responses are still insufficiently described. We analyzed the epigenetic impact of ambient PM2.5 from biomass combustion on the methylome of primary human bronchial epithelial BEAS-2B cells using the Illumina HumanMethylation450 BeadChip. The transcriptome was determined by the Affymetrix HG-U133 Plus 2.0 Array. PM2.5 induced genome wide alterations of the DNA methylation pattern, including differentially methylated CpGs in the promoter region associated with CpG islands. Gene ontology analysis revealed that differentially methylated genes were significantly clustered in pathways associated with the extracellular matrix, cellular adhesion, function of GTPases, and responses to extracellular stimuli, or were involved in ion binding and shuttling. Differential methylations also affected tandem repeats. Additionally, 45 different miRNA CpG loci showed differential DNA methylation, most of them proximal to their promoter. These miRNAs are functionally relevant for lung cancer, inflammation, asthma, and other PM-associated diseases. Correlation of the methylome and transcriptome demonstrated a clear bias toward transcriptional activation by hypomethylation. Genes that exhibited both differential methylation and expression were functionally linked to cytokine and immune responses, cellular motility, angiogenesis, inflammation, wound healing, cell growth, differentiation and development, or responses to exogenous matter. Disease ontology of differentially methylated and expressed genes indicated their prominent role in lung cancer and their participation in dominant cancer related signaling pathways. Thus, in lung epithelial cells, PM2.5 alters the methylome of genes and noncoding transcripts or elements that might be relevant for PM- and lung-associated diseases

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch
Notes
Epigenetics. - 12, 9 (2017) , 779-792, ISSN: 1559-2308

Event
Veröffentlichung
(where)
Freiburg
(who)
Universität
(when)
2019
Creator
Contributor
Pharmazeutische und Medizinische Chemie, Arbeitskreis Prof. Dr. Irmgard Merfort
Albert-Ludwigs-Universität Freiburg. Pharmazeutische Bioinformatik
FRIAS Natur- und Lebenswissenschaften, Medizin und Ingenieurwissenschaften

DOI
10.1080/15592294.2017.1356555
URN
urn:nbn:de:bsz:25-freidok-1393735
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
14.08.2025, 10:57 AM CEST

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Time of origin

  • 2019

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