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.
777-788
Seumois, Grégory
0be7d3d6-5526-458c-aa5c-cce52410a2ed
Chavez, Lukas
84f58e4d-a3e4-4b69-87d4-5783f15580cb
Gerasimova, Anna
9172f558-68dd-4d71-9e00-ce5314681145
Lienhard, Matthias
091f6ce4-3f11-4820-86af-e3f0b3c5a500
Omran, Nada
cde20d0c-fd4b-4f9e-8ee2-30a74f310e16
Kalinke, Lukas
841230f7-4bd8-4c69-8133-628702ef8956
Vedanayagam, Maria
45579461-2239-47e7-85ca-38c2bc4d5957
Ganesan, Asha Purnima V
d13c0d4a-9b75-430d-921e-a00fa63f1f45
Chawla, Ashu
a7528db3-560b-4688-ad38-cbf077bfffb7
Djukanović, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Ansel, K Mark
419a9477-acf1-411b-b9d4-a9504bb18bce
Peters, Bjoern
c49863c8-d2c6-4db4-9d2c-72a7c0cbe117
Rao, Anjana
d22da889-4e55-4fb5-9818-bd47dc12348a
Vijayanand, Pandurangan
79514f33-66cf-47cc-a8fa-46bbfc21b7d1
1 August 2014
Seumois, Grégory
0be7d3d6-5526-458c-aa5c-cce52410a2ed
Chavez, Lukas
84f58e4d-a3e4-4b69-87d4-5783f15580cb
Gerasimova, Anna
9172f558-68dd-4d71-9e00-ce5314681145
Lienhard, Matthias
091f6ce4-3f11-4820-86af-e3f0b3c5a500
Omran, Nada
cde20d0c-fd4b-4f9e-8ee2-30a74f310e16
Kalinke, Lukas
841230f7-4bd8-4c69-8133-628702ef8956
Vedanayagam, Maria
45579461-2239-47e7-85ca-38c2bc4d5957
Ganesan, Asha Purnima V
d13c0d4a-9b75-430d-921e-a00fa63f1f45
Chawla, Ashu
a7528db3-560b-4688-ad38-cbf077bfffb7
Djukanović, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Ansel, K Mark
419a9477-acf1-411b-b9d4-a9504bb18bce
Peters, Bjoern
c49863c8-d2c6-4db4-9d2c-72a7c0cbe117
Rao, Anjana
d22da889-4e55-4fb5-9818-bd47dc12348a
Vijayanand, Pandurangan
79514f33-66cf-47cc-a8fa-46bbfc21b7d1
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), .
(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.
Text
Seumois-2014-Epigenomic-analysis-of-primary-huma
- Accepted Manuscript
More information
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
Catalogue record
Date deposited: 11 Dec 2019 17:30
Last modified: 17 Mar 2024 02:34
Export record
Altmetrics
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
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics