Genome wide DNA methylation and Hydroxymethylation of F1 mouse lung prenatally exposed to house dust mite

We used a mouse model of allergic lung disease to examine the effects of pre- and perinatal house dust mite (HDM) allergen exposure on offspring lung phenotypic and transcriptional outcomes. We showed that maternal HDM exposure (F0) acts synergistically with adult HDM exposure, leading to enhanced airway hyperresponsiveness (AHR) and lung inflammation when compared to mice exposed solely in adulthood. To examine the role of epigenetic inheritance of asthma susceptibility induced by maternal HDM exposure, we utilized a genome-wide MeDIP-seq and hMeDIP-seq analysis to identify genes differentially methylated (DMG) and hydroxymethylated (DHG), and their association with the enhanced AHR. In addition, we validated the relationship between DNA methylation and mRNA expression of the DMGs and DHGs in the male progenies. Overall design: We compared the lung DNA methylation and hydroxymethylation patterns from F1 progenies from dams exposed to saline or HDM (F0-Saline_F1-HDM or F0-HDM_F1-HDM) when compared to their counterparts who did not received HDM challenges in their adulthood (F0-Saline_F1-Saline or F0-HDM_F1-Saline). Genomic DNA from each treatment group (pooled from mice of 3 individual dams) was subject for MeDIP-seq and hMeDIP-seq. Validation of airway responsiveness, cell counts and relative gene expression were performed on six mice per treatment group.