Dataset Information
Profiling of H3K27Ac Reveals the Influence of Asthma on the Epigenome of the Airway Epithelium.
Ontology highlight
ABSTRACT: 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.
SUBMITTER: McErlean P
PROVIDER: S-EPMC7758344 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Profiling of H3K27Ac Reveals the Influence of Asthma on the Epigenome of the Airway Epithelium.
Frontiers in genetics 20201210
<h4>Background</h4>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.<h4>Methods</h4>We piloted genome-wide profiling of the enhancer-associated histone modification H3K27ac in BECs from people with asthma (<i>n</i> = 4) and healthy controls (<i>n</i> = 3).<h4>Results</h4>We identified <i>n</i> = 4,321 (FDR < 0.05) regions exhibiting differential H3K27ac ...[more]
