title: Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility.
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.
authors.affiliation: 1] La Jolla Institute for Allergy & Immunology, La Jolla, California, USA. [2] Clinical and Experimental Sciences, Southampton National Institute for Health Research Respiratory Biomedical Research Unit, University of Southampton, Faculty of Medicine, Southampton, UK. [3] University of California San Francisco, San Francisco, California, USA. [4].
authors.forename: Grégory
authors.initials: G
authors.lastname: Seumois
authors.affiliation: 1] La Jolla Institute for Allergy & Immunology, La Jolla, California, USA. [2].
authors.forename: Lukas
authors.initials: L
authors.lastname: Chavez
authors.affiliation: 1] La Jolla Institute for Allergy & Immunology, La Jolla, California, USA. [2].
authors.forename: Anna
authors.initials: A
authors.lastname: Gerasimova
authors.affiliation: La Jolla Institute for Allergy & Immunology, La Jolla, California, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Lienhard
authors.affiliation: Clinical and Experimental Sciences, Southampton National Institute for Health Research Respiratory Biomedical Research Unit, University of Southampton, Faculty of Medicine, Southampton, UK.
authors.forename: Nada
authors.initials: N
authors.lastname: Omran
authors.affiliation: Clinical and Experimental Sciences, Southampton National Institute for Health Research Respiratory Biomedical Research Unit, University of Southampton, Faculty of Medicine, Southampton, UK.
authors.forename: Lukas
authors.initials: L
authors.lastname: Kalinke
authors.affiliation: Clinical and Experimental Sciences, Southampton National Institute for Health Research Respiratory Biomedical Research Unit, University of Southampton, Faculty of Medicine, Southampton, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Vedanayagam
authors.affiliation: Clinical and Experimental Sciences, Southampton National Institute for Health Research Respiratory Biomedical Research Unit, University of Southampton, Faculty of Medicine, Southampton, UK.
authors.forename: Asha Purnima V
authors.initials: AP
authors.lastname: Ganesan
authors.affiliation: La Jolla Institute for Allergy & Immunology, La Jolla, California, USA.
authors.forename: Ashu
authors.initials: A
authors.lastname: Chawla
authors.affiliation: Clinical and Experimental Sciences, Southampton National Institute for Health Research Respiratory Biomedical Research Unit, University of Southampton, Faculty of Medicine, Southampton, UK.
authors.forename: Ratko
authors.initials: R
authors.lastname: Djukanović
authors.affiliation: University of California San Francisco, San Francisco, California, USA.
authors.forename: K Mark
authors.initials: KM
authors.lastname: Ansel
authors.affiliation: La Jolla Institute for Allergy & Immunology, La Jolla, California, USA.
authors.forename: Bjoern
authors.identifier: 0000000284576693
authors.initials: B
authors.lastname: Peters
authors.affiliation: 1] La Jolla Institute for Allergy & Immunology, La Jolla, California, USA. [2] Sanford Consortium for Regenerative Medicine, La Jolla, California, USA. [3] Department of Pharmacology, University of California San Diego, San Diego, California, USA. [4] University of California San Diego Moores Cancer Center, San Diego, California, USA.
authors.forename: Anjana
authors.initials: A
authors.lastname: Rao
authors.affiliation: 1] La Jolla Institute for Allergy & Immunology, La Jolla, California, USA. [2] Clinical and Experimental Sciences, Southampton National Institute for Health Research Respiratory Biomedical Research Unit, University of Southampton, Faculty of Medicine, Southampton, UK. [3] University of California San Francisco, San Francisco, California, USA.
authors.forename: Pandurangan
authors.initials: P
authors.lastname: Vijayanand
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics* / Q000276:immunology*; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D057890:Epigenomics; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006657:Histones / Q000235:genetics / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D017423:Sequence Analysis, RNA; D020825:T-Box Domain Proteins / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D055815:Young Adult; D000098815:T-bet Transcription Factor
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D006657:Histones; D035683:MicroRNAs; C493729:Runx3 protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor