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Method: We used a fully validated micro-scaled (100.000 cells) and multiplex-chromatin immunoprecipitation experiments to capture genomic regions enriched in Histone 3 Lysine 4 dimethylation (H3K4me2). Using high throughput next generation sequencing, we have mapped the genome-wide distribution of promoters and enhancers (enriched with H3K4me2) in naïve, CCR4+(Th2-enriched) and CCR4-(Th2-depleted, Th1-enriched) cells from 12 healthy and 12 asthmatic subjects.

Results: We identified enhancers with known and potential roles in the normal differentiation of human Th1 and Th2 cells. In addition, we discovered disease-specific T cell enhancers that differ between healthy and asthmatic individuals. Enhancers that gained the histone 3 lysine 4 dimethyl (H3K4me2) mark during Th2 development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs …