Abstract
Background: Epigenetic mechanisms may play a role in which PAHs exert its adverse effects in childhood asthma. However, the underlying molecular mechanism remain to be fully elucidated. This study aimed to investigate this process in view of cellular metabolism, especially one carbon metabolism. Methods: Fifty asthmatic children and fifty control subjects were recruited in this study. Serum IgE and IL-17A was detected by ELISA assay. Serum PAHs levels were measured by GC-MS. One carbon-related metabolites were determined by UPLC-Orbitrap-MS. Blood DNA methylation in long interspersed nucleotide element-1 (LINE-1) was analyzed by bisulfite sequencing PCR. ChIP assays were used to examine H3K4me3 modifications on IL-17A gene. Multivariable linear regression was performed to evaluate the associates between PAHs and DNA methylation and histone methylation mediated by one carbon metabolism. Results: The asthmatic group presented significantly higher total serum IgE and IL-17A levels. Serum Fla was associated with childhood asthma. The asthmatic group displayed a significantly decreasing in SAM abundance and a smaller but corresponding decrease in SAH, which indicated the increasing conversion from SAM to SAH and the elevated capacity of methylation reactions. Fla had a great effect on one carbon metabolites, especially SAH, SAM and Ser, which exerted significant mediation effects between the Fla level and asthma. What’s more, Fla had a positive effect on LINE-1 DNA methylation (β=0.395, P=0.000) and H3K4 tri-methylation level in the IL-17A promoter region(β=0.293, P=0.002). We did find significant mediation effect between serum Fla and asthma by LINE-1 DNA methylation and H3K4me3 level in the IL-17A promoter region.Conclusion: PAHs disturbed one carbon metabolism to influence the methyl group refill of DNA methylation and histone methylation, which may elevate serum IL-17A level in asthmatic children.
Histone Methylation Dynamics and Gene Regulation Occur through the Sensing of One-Carbon Metabolism
