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

Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility
Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility
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.
1529-2908
777-788
Seumois, Grégory
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Chavez, Lukas
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Gerasimova, Anna
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Lienhard, Matthias
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Omran, Nada
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Kalinke, Lukas
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Vedanayagam, Maria
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Ganesan, Asha Purnima V
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Chawla, Ashu
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Djukanović, Ratko
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Ansel, K Mark
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Peters, Bjoern
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Rao, Anjana
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Vijayanand, Pandurangan
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Seumois, Grégory
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Chavez, Lukas
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Gerasimova, Anna
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Lienhard, Matthias
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Omran, Nada
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Kalinke, Lukas
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Vedanayagam, Maria
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Ganesan, Asha Purnima V
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Chawla, Ashu
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Djukanović, Ratko
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Ansel, K Mark
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Peters, Bjoern
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Rao, Anjana
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Vijayanand, Pandurangan
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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).

Record type: Article

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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Seumois-2014-Epigenomic-analysis-of-primary-huma - Accepted Manuscript
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e-pub ahead of print date: 6 July 2014
Published date: 1 August 2014

Identifiers

Local EPrints ID: 436482
URI: http://eprints.soton.ac.uk/id/eprint/436482
ISSN: 1529-2908
PURE UUID: e88d3b44-89b3-4432-9a10-0b150bc68492
ORCID for Ratko Djukanović: ORCID iD orcid.org/0000-0001-6039-5612

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Date deposited: 11 Dec 2019 17:30
Last modified: 17 Dec 2019 02:03

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Contributors

Author: Grégory Seumois
Author: Lukas Chavez
Author: Anna Gerasimova
Author: Matthias Lienhard
Author: Nada Omran
Author: Lukas Kalinke
Author: Maria Vedanayagam
Author: Asha Purnima V Ganesan
Author: Ashu Chawla
Author: K Mark Ansel
Author: Bjoern Peters
Author: Anjana Rao
Author: Pandurangan Vijayanand

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