Imperial College London
Alternate

ProfessorSebastianJohnston

Faculty of Medicine, National Heart & Lung Institute

Asthma UK Clinical Chair
 
 
 
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Contact

 

+44 (0)7931 376 544s.johnston

 
 
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Assistant

 

Mr Christophe Tytgat +44 (0)20 7594 3849

 
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Location

 

343Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{McErlean:2018:10.1101/282889,
author = {McErlean, P and Kelly, A and Dhariwal, J and Kirtland, M and Watson, J and Ranz, Jimenez I and Saxena, A and Cousins, D and Solari, R and Edwards, M and Johnston, S and Lavender, P},
doi = {10.1101/282889},
journal = {Biorxiv},
title = {Genome-wide profiling of an enhancer-associated histone modification reveals the influence of asthma on the epigenome of the airway epithelium.},
url = {http://dx.doi.org/10.1101/282889},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Asthma is a chronic airway disease driven by complex genetic-environmental interactions. The role of epigenetic modifications in bronchial epithelial cells (BECs) in asthma is poorly understood. We undertook genome-wide profiling of the enhancer-associated histone modification H3K27ac in BECs from people with asthma and healthy controls. We identified 49,903 regions exhibiting differential H3K27ac enrichment in asthma, clustered at genes associated with type-2-high asthma (CLCA1) and epithelial processes (EMT). Asthma dramatically influenced the BEC enhancer landscape and we identified asthma-associated Super-Enhancers encompassing genes encoding transcription factors (TP63) and enzymes regulating lipid metabolism (NOX4). We integrated published protein, epigenomic and transcriptomic datasets and identified epithelium-specific transcription factors associated with H3K27ac in asthma (TP73) and dynamic relationships between asthma-associated changes in H3K27ac, DNA methylation, genetic susceptibility and transcriptional profiles. Finally, we used a CRISPR-based approach to recapitulate the H3K27ac-asthma landscape in vitro and provide proof of principal that asthma-associated gene expression (SERPINB2) is driven in part by aberrant histone acetylation, validating the combination of genome-wide and epigenome-editing approaches in deciphering the molecular mechanisms underlying asthma pathogenesis.
AU  - McErlean,P
AU  - Kelly,A
AU  - Dhariwal,J
AU  - Kirtland,M
AU  - Watson,J
AU  - Ranz,Jimenez I
AU  - Saxena,A
AU  - Cousins,D
AU  - Solari,R
AU  - Edwards,M
AU  - Johnston,S
AU  - Lavender,P
DO  - 10.1101/282889
PY  - 2018///
TI  - Genome-wide profiling of an enhancer-associated histone modification reveals the influence of asthma on the epigenome of the airway epithelium.
T2  - Biorxiv
UR  - http://dx.doi.org/10.1101/282889
ER  -
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