Profiling of H3K27Ac Reveals the Influence of Asthma on the Epigenome of the Airway Epithelium
BackgroundAsthma 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.MethodsWe piloted genome-wide profiling of the enhancer-associated histone modification H3K27ac...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2020.585746/full |
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| author | Peter McErlean Peter McErlean Audrey Kelly Audrey Kelly Jaideep Dhariwal Jaideep Dhariwal Max Kirtland Max Kirtland Julie Watson Julie Watson Ismael Ranz Ismael Ranz Janet Smith Alka Saxena David J. Cousins David J. Cousins Antoon Van Oosterhout Roberto Solari Roberto Solari Michael R. Edwards Michael R. Edwards Sebastian L. Johnston Sebastian L. Johnston Paul Lavender Paul Lavender |
| author_facet | Peter McErlean Peter McErlean Audrey Kelly Audrey Kelly Jaideep Dhariwal Jaideep Dhariwal Max Kirtland Max Kirtland Julie Watson Julie Watson Ismael Ranz Ismael Ranz Janet Smith Alka Saxena David J. Cousins David J. Cousins Antoon Van Oosterhout Roberto Solari Roberto Solari Michael R. Edwards Michael R. Edwards Sebastian L. Johnston Sebastian L. Johnston Paul Lavender Paul Lavender |
| author_sort | Peter McErlean |
| collection | DOAJ |
| description | BackgroundAsthma 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.MethodsWe piloted genome-wide profiling of the enhancer-associated histone modification H3K27ac in BECs from people with asthma (n = 4) and healthy controls (n = 3).ResultsWe 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).ConclusionOur small pilot study validates genome-wide approaches for deciphering epigenetic mechanisms underlying asthma pathogenesis in the airways. |
| first_indexed | 2024-12-17T22:58:47Z |
| format | Article |
| id | doaj.art-7cb4bd32b5e64d748ae7401e5f6f18c3 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-17T22:58:47Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-7cb4bd32b5e64d748ae7401e5f6f18c32022-12-21T21:29:27ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-12-011110.3389/fgene.2020.585746585746Profiling of H3K27Ac Reveals the Influence of Asthma on the Epigenome of the Airway EpitheliumPeter McErlean0Peter McErlean1Audrey Kelly2Audrey Kelly3Jaideep Dhariwal4Jaideep Dhariwal5Max Kirtland6Max Kirtland7Julie Watson8Julie Watson9Ismael Ranz10Ismael Ranz11Janet Smith12Alka Saxena13David J. Cousins14David J. Cousins15Antoon Van Oosterhout16Roberto Solari17Roberto Solari18Michael R. Edwards19Michael R. Edwards20Sebastian L. Johnston21Sebastian L. Johnston22Paul Lavender23Paul Lavender24Peter Gorer Department of Immunobiology, King’s College London, London, United KingdomAsthma UK Centre in Allergic Mechanisms of Asthma, London, United KingdomPeter Gorer Department of Immunobiology, King’s College London, London, United KingdomAsthma UK Centre in Allergic Mechanisms of Asthma, London, United KingdomAsthma UK Centre in Allergic Mechanisms of Asthma, London, United KingdomAirway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, United KingdomPeter Gorer Department of Immunobiology, King’s College London, London, United KingdomAsthma UK Centre in Allergic Mechanisms of Asthma, London, United KingdomPeter Gorer Department of Immunobiology, King’s College London, London, United KingdomAsthma UK Centre in Allergic Mechanisms of Asthma, London, United KingdomPeter Gorer Department of Immunobiology, King’s College London, London, United KingdomAsthma UK Centre in Allergic Mechanisms of Asthma, London, United KingdomGlaxoSmithKline Allergic Inflammation Discovery Performance Unit, Respiratory Therapy Area, Stevenage, United KingdomGenomics Platform, Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust, London, United KingdomAsthma UK Centre in Allergic Mechanisms of Asthma, London, United KingdomNational Institute for Health Research (NIHR) Respiratory Biomedical Research Unit, Department of Infection, Immunity & Inflammation, Leicester Institute for Lung Health, University of Leicester, Leicester, United KingdomGlaxoSmithKline Allergic Inflammation Discovery Performance Unit, Respiratory Therapy Area, Stevenage, United KingdomAsthma UK Centre in Allergic Mechanisms of Asthma, London, United KingdomAirway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, United KingdomAsthma UK Centre in Allergic Mechanisms of Asthma, London, United KingdomAirway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, United KingdomAsthma UK Centre in Allergic Mechanisms of Asthma, London, United KingdomAirway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, United KingdomPeter Gorer Department of Immunobiology, King’s College London, London, United KingdomAsthma UK Centre in Allergic Mechanisms of Asthma, London, United KingdomBackgroundAsthma 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.MethodsWe piloted genome-wide profiling of the enhancer-associated histone modification H3K27ac in BECs from people with asthma (n = 4) and healthy controls (n = 3).ResultsWe 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).ConclusionOur small pilot study validates genome-wide approaches for deciphering epigenetic mechanisms underlying asthma pathogenesis in the airways.https://www.frontiersin.org/articles/10.3389/fgene.2020.585746/fullasthmaepigeneticsH3K27ac—Histone 3 lysine 27 acetylationchromatinbronchial epithelial cellslung |
| spellingShingle | Peter McErlean Peter McErlean Audrey Kelly Audrey Kelly Jaideep Dhariwal Jaideep Dhariwal Max Kirtland Max Kirtland Julie Watson Julie Watson Ismael Ranz Ismael Ranz Janet Smith Alka Saxena David J. Cousins David J. Cousins Antoon Van Oosterhout Roberto Solari Roberto Solari Michael R. Edwards Michael R. Edwards Sebastian L. Johnston Sebastian L. Johnston Paul Lavender Paul Lavender Profiling of H3K27Ac Reveals the Influence of Asthma on the Epigenome of the Airway Epithelium Frontiers in Genetics asthma epigenetics H3K27ac—Histone 3 lysine 27 acetylation chromatin bronchial epithelial cells lung |
| title | Profiling of H3K27Ac Reveals the Influence of Asthma on the Epigenome of the Airway Epithelium |
| title_full | Profiling of H3K27Ac Reveals the Influence of Asthma on the Epigenome of the Airway Epithelium |
| title_fullStr | Profiling of H3K27Ac Reveals the Influence of Asthma on the Epigenome of the Airway Epithelium |
| title_full_unstemmed | Profiling of H3K27Ac Reveals the Influence of Asthma on the Epigenome of the Airway Epithelium |
| title_short | Profiling of H3K27Ac Reveals the Influence of Asthma on the Epigenome of the Airway Epithelium |
| title_sort | profiling of h3k27ac reveals the influence of asthma on the epigenome of the airway epithelium |
| topic | asthma epigenetics H3K27ac—Histone 3 lysine 27 acetylation chromatin bronchial epithelial cells lung |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2020.585746/full |
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