AUTHOR=McErlean Peter , Kelly Audrey , Dhariwal Jaideep , Kirtland Max , Watson Julie , Ranz Ismael , Smith Janet , Saxena Alka , Cousins David J. , Van Oosterhout Antoon , Solari Roberto , Edwards Michael R. , Johnston Sebastian L. , Lavender Paul 

TITLE=Profiling of H3K27Ac Reveals the Influence of Asthma on the Epigenome of the Airway Epithelium

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.585746

DOI=10.3389/fgene.2020.585746

ISSN=1664-8021

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>We piloted genome-wide profiling of the enhancer-associated histone modification H3K27ac in BECs from people with asthma (<italic>n</italic> = 4) and healthy controls (<italic>n</italic> = 3).</p></sec><sec><title>Results</title><p>We identified <italic>n</italic> = 4,321 (FDR &lt; 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 (<italic>TP63</italic>) and enzymes regulating lipid metabolism (<italic>PTGS1</italic>). We integrated published datasets to identify epithelium-specific transcription factors associated with H3K27ac in asthma (<italic>TP73</italic>) 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 <italic>in vitro</italic> by identifying guide-RNAs capable of targeting acetylation to asthma DERs and inducing gene expression (<italic>TLR3</italic>).</p></sec><sec><title>Conclusion</title><p>Our small pilot study validates genome-wide approaches for deciphering epigenetic mechanisms underlying asthma pathogenesis in the airways.</p></sec>