Seumois, Grégory, Chavez, Lukas, Gerasimova, Anna, Lienhard, Matthias, Omran, Nada, Kalinke, Lukas, Vedanayagam, Maria, Ganesan, Asha Purnima V, Chawla, Ashu, Djukanović, Ratko, Ansel, K Mark, Peters, Bjoern, Rao, Anjana and Vijayanand, Pandurangan (2014) Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility. Nature Immunology, 15 (8), 777-788. (doi:10.1038/ni.2937).
Abstract
A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4+ T cells that produce type 2 cytokines (TH2 cells). By mapping genome-wide histone modification profiles for subsets of T cells isolated from peripheral blood of healthy and asthmatic individuals, we identified enhancers with known and potential roles in the normal differentiation of human TH1 cells and TH2 cells. We discovered disease-specific enhancers in T cells that differ between healthy and asthmatic individuals. Enhancers that gained the histone H3 Lys4 dimethyl (H3K4me2) mark during TH2 cell development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs), which supported a pathogenic role for TH2 cells in asthma. In silico analysis of cell-specific enhancers revealed transcription factors, microRNAs and genes potentially linked to human TH2 cell differentiation. Our results establish the feasibility and utility of enhancer profiling in well-defined populations of specialized cell types involved in disease pathogenesis.
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- Current Faculties > Faculty of Medicine > Clinical and Experimental Sciences > Tissue Infection and Repair
Clinical and Experimental Sciences > Tissue Infection and Repair - Current Faculties > Faculty of Medicine > Clinical and Experimental Sciences > Allergy and Inflammation Research
Clinical and Experimental Sciences > Allergy and Inflammation Research - Faculties (pre 2018 reorg) > Faculty of Natural and Environmental Sciences (pre 2018 reorg) > Institute for Life Sciences (pre 2018 reorg)
Current Faculties > Faculty of Environmental and Life Sciences > Institute for Life Sciences > Institute for Life Sciences (pre 2018 reorg)
Institute for Life Sciences > Institute for Life Sciences (pre 2018 reorg) - Current Faculties > Faculty of Medicine > Clinical and Experimental Sciences
Clinical and Experimental Sciences - Faculties (pre 2018 reorg) > Faculty of Medicine (pre 2018 reorg) > NIHR Southampton Respiratory Biomedical Research Unit (pre 2018 reorg)
Current Faculties > Faculty of Medicine > NIHR Southampton Biomedical Research Centre > NIHR Southampton Respiratory Biomedical Research Unit (pre 2018 reorg)
NIHR Southampton Biomedical Research Centre > NIHR Southampton Respiratory Biomedical Research Unit (pre 2018 reorg)
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