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Epigenetics. 2017 Sep;12(9):779-792. doi: 10.1080/15592294.2017.1356555. Epub 2017 Oct 27.

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

Author information

1
a Pharmaceutical Biology and Biotechnology, Albert-Ludwigs-University Freiburg , Freiburg , Germany.
2
b Pharmaceutical Bioinformatics, Albert-Ludwigs-University Freiburg , Freiburg , Germany.
3
c Department of Rheumatology and Clinical Immunology , Charité University Hospital Berlin , Germany.
4
d Pharmaceutical Bioinformatics and Freiburg Institute for Advanced Studies (FRIAS), Albert-Ludwigs University Freiburg , Freiburg , Germany.

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.

KEYWORDS:

biomass combustion; disease ontology; methylome; particulate matter; transcriptome

PMID:
28742980
PMCID:
PMC5739103
DOI:
10.1080/15592294.2017.1356555
[Indexed for MEDLINE]
Free PMC Article

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