D3.114 - Characterization on genome-wide profile of H3K4me2 histone methylation in mouse asthmatic lung induced by Alt a 1

Alternaria alternata is considered one of the most important fungal allergens worldwide and is associated with severe asthma and respiratory status. Alt a1  is the major allergen related to Alternaria-induced asthma. Epigenetic marks, including histone methylation within chromatin, translate environmental cues into changes in gene regulation. Therefore, this study aims to understand changes in H3K4me2 histone methylation signature under allergic sensitization, to help explore the mechanisms underlying asthma induced by Alt a 1.

Chromatin immunoprecipitation sequencing (ChIP-seq) was used to obtain the genome-wide profile in mouse skin suffering from allergic sensitization triggered by Ara h 2 with lipids.

Here, peaks identified in the asthma group exhibited a globally higher signal distribution than those in the healthy group (Wilcoxon rank-sum test, p < 2.2×10⁻¹⁶), suggesting increased overall enrichment of this histone mark in the disease state. ChIP-seq analysis revealed 140,742 differentially more enriched regions (DER) in asthmatic lung and 94,875 DERs in healthy lung. These DERs were primarily located in distal intergenic regions (37.18%), introns (40.36%), and promoters (< 2 kb of the TSS, 4.8%). The KEGG enrichment analysis showed genes annotated from DERs in asthmatic lung related to promoter regions were significantly (FDR = 0.052) enriched in 3 immune system-related pathways, including leukocyte transendothelial migration (FDR = 0.0073), Th1 and Th2 cell differentiation (FDR = 0.0051) and hematopoietic cell lineage (FDR = 0.0051).

This study provides the genome-wide characterization of H3K4me2 profiles in mouse lung suffering from asthma triggered by Alt a 1. Alt a 1 exposure induces the H3K4me2 modification in mouse lung. Functional analysis suggests that DERs with higher levels of H3K4me2 play a critical role in regulating immune-related pathways. Moreover, these results will provide valuable resources for mechanism studies of gene regulation in lung sensitization underlying asthma induced by Alt a 1.