title: Chemical allergen induced perturbations of the mouse lymph node DNA methylome.
abstract: Epigenetic regulation of gene expression plays a pivotal role in the orchestration of immune responses and may determine the vigor, quality, or longevity of such responses. Chemical allergens can be divided into two categories: skin sensitizing chemicals associated with allergic contact dermatitis, and chemicals that cause sensitization of the respiratory tract and occupational asthma. In mice, these are characterized by different T helper cell responses. To explore the regulation and maintenance of these divergent responses, mice were exposed to 2,4-dinitrochlorobenzene (DNCB, a contact allergen) or trimellitic anhydride (TMA, a respiratory allergen). DNA from draining lymph nodes was processed for methylated DNA immunoprecipitation followed by hybridization to a whole-genome DNA promoter array. 6319 differently methylated regions (DMRs) were identified following DNCB treatment, whereas 2178 DMRs were measured following TMA treatment, with approximately half of the TMA DMRs common to DNCB. When limited to promoter region-associated DMRs, 637 genes were uniquely associated with DNCB-induced DMRs but only 164 genes were unique to TMA DMRs. Promoter-associated DMRs unique to either DNCB or TMA were generally hypomethylated whereas DMRs common to both allergens tended to be hypermethylated. Pathway analyses highlighted a number of immune-related pathways, including chemokine and cytokine signaling. These data demonstrate that chemical allergen exposure results in characteristic patterns of DNA methylation indicative of epigenetic regulation of the allergic response.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, UK.
authors.forename: Victoria Louise
authors.initials: VL
authors.lastname: Chapman
authors.forename: Tulipan
authors.initials: T
authors.lastname: Zollinger
authors.forename: Rémi
authors.initials: R
authors.lastname: Terranova
authors.forename: Jonathan
authors.initials: J
authors.lastname: Moggs
authors.forename: Ian
authors.initials: I
authors.lastname: Kimber
authors.forename: Rebecca Jane
authors.initials: RJ
authors.lastname: Dearman
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D004247:DNA / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects* / Q000235:genetics; D004137:Dinitrochlorobenzene / Q000737:chemistry / Q000633:toxicity*; D044127:Epigenesis, Genetic; D005260:Female; D055106:Genome-Wide Association Study; D047468:Immunoprecipitation; D008198:Lymph Nodes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008807:Mice, Inbred BALB C; D010796:Phthalic Anhydrides / Q000737:chemistry / Q000633:toxicity*; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000485:Allergens; D004137:Dinitrochlorobenzene; D010796:Phthalic Anhydrides; C015559:trimellitic anhydride; D004247:DNA
keywords: DNA methylation; chemical allergy; epigenetic; mouse lymph node