Imperial College London

DrMichaelEdwards

Faculty of MedicineNational Heart & Lung Institute

Senior Lecturer
 
 
 
//

Contact

 

+44 (0)20 7594 5291michael.edwards

 
 
//

Location

 

346Norfolk PlaceSt Mary's Campus

//

Summary

 

Publications

Citation

BibTex format

@article{McErlean:2020:10.3389/fgene.2020.585746,
author = {McErlean, P and Kelly, A and Dhariwal, J and Kirtland, M and Watson, J and Ranz, I and Smith, J and Saxena, A and Cousins, DJ and Van, Oosterhout A and Solari, R and Edwards, MR and Johnston, SL and Lavender, P},
doi = {10.3389/fgene.2020.585746},
journal = {Frontiers in Genetics},
pages = {1--12},
title = {Profiling of H3K27Ac reveals the influence of asthma on the epigenome of the airway epithelium},
url = {http://dx.doi.org/10.3389/fgene.2020.585746},
volume = {11},
year = {2020}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Background: 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.Methods: We piloted genome-wide profiling of the enhancer-associated histone modification H3K27ac in BECs from people with asthma (n = 4) and healthy controls (n = 3).Results: We identified n = 4,321 (FDR < 0.05) regions exhibiting differential H3K27ac enrichment between asthma and health, clustering at genes associated predominately with epithelial processes (EMT). We identified initial evidence of asthma-associated Super-Enhancers encompassing genes encoding transcription factors (TP63) and enzymes regulating lipid metabolism (PTGS1). We integrated published datasets to identify epithelium-specific transcription factors associated with H3K27ac in asthma (TP73) and identify initial relationships between asthma-associated changes in H3K27ac and transcriptional profiles. Finally, we investigated the potential of CRISPR-based approaches to functionally evaluate H3K27ac-asthma landscape in vitro by identifying guide-RNAs capable of targeting acetylation to asthma DERs and inducing gene expression (TLR3).Conclusion: Our small pilot study validates genome-wide approaches for deciphering epigenetic mechanisms underlying asthma pathogenesis in the airways.
AU - McErlean,P
AU - Kelly,A
AU - Dhariwal,J
AU - Kirtland,M
AU - Watson,J
AU - Ranz,I
AU - Smith,J
AU - Saxena,A
AU - Cousins,DJ
AU - Van,Oosterhout A
AU - Solari,R
AU - Edwards,MR
AU - Johnston,SL
AU - Lavender,P
DO - 10.3389/fgene.2020.585746
EP - 12
PY - 2020///
SN - 1664-8021
SP - 1
TI - Profiling of H3K27Ac reveals the influence of asthma on the epigenome of the airway epithelium
T2 - Frontiers in Genetics
UR - http://dx.doi.org/10.3389/fgene.2020.585746
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000601278400001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - https://www.frontiersin.org/articles/10.3389/fgene.2020.585746/full
UR - http://hdl.handle.net/10044/1/92321
VL - 11
ER -