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  Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility

Seumois, G., Chavez, L., Gerasimova, A., Lienhard, M., Omran, N., Kalinke, L., et al. (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.

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Seumois, Grégory , Author
Chavez, Lukas1, Author              
Gerasimova, Anna, Author
Lienhard, Matthias2, Author              
Omran, Nada, Author
Kalinke, Lukas , Author
Vedanayagam, Maria, Author
Ganesan, Asha Purnima V. , Author
Chawla, Ashu , Author
Djukanović, Ratko , Author
Ansel, K. Mark, Author
Peters, Bjoern , Author
Rao, Anjana, Author
Vijayanand, Pandurangan , Author
Affiliations:
1Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              
2Bioinformatics (Ralf Herwig), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479648              

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 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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Language(s): eng - English
 Dates: 2014-07-062014-08
 Publication Status: Published in print
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1038/ni.2937
PMC: PMC4140783
PMID: 24997565
 Degree: -

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Title: Nature Immunology
  Other : Nat. Immunol.
Source Genre: Journal
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Publ. Info: New York, NY : Nature America Inc.
Pages: - Volume / Issue: 15 (8) Sequence Number: - Start / End Page: 777 - 788 Identifier: ISSN: 1529-2916 (online)