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TET1 transcriptionally responded to HDM extract and regulated the expression of genes involved in asthma in human bronchial epithelial cells (HBECs). How TET1 regulates the expression of these genes, however, is unknown. To this end, we measured mRNA expression, DNA methylation, chromatin accessibility, and histone modifications in control and TET1 knockdown HBECs treated or untreated with HDM extract. Throughout our analyses of multiomics data, we detected significant similarities between the effects of TET1 knockdown alone and the effects of HDM treatment alone, all enriched for asthma-related genes and pathways. One especially striking pattern was that both TET1 knockdown and HDM treatment generally led to decreased chromatin accessibility at many of the same genomic loci. Transcription factor enrichment analyses indicated that altered chromatin accessibility following the loss of TET1 may affect, or be affected by, CCCTC-binding factor and CCAAT-enhancer-binding protein binding. Analysis of H3K27ac levels and comparison with existing datasets suggested a potential impact of TET1 on enhancer activity. TET1 loss also led to changes in DNA methylation, but these changes were generally in regions where accessibility was not changing. Lastly, more significant transcriptomic changes were observed in HBEC cells with TET1 knockdown compared to control cells following HDM challenges. Collectively, our data suggest that TET1 regulates gene expression through distinct mechanisms across various genomic regions in airway epithelial cells, restricting transcriptomic responses to allergen and potentially protecting against the development of asthma.<\/jats:p>","DOI":"10.1093\/eep\/dvaf007","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T17:23:43Z","timestamp":1742405023000},"source":"Crossref","is-referenced-by-count":2,"title":["Silencing\n                    <i>TET1<\/i>\n                    expression alters the epigenomic landscape and amplifies transcriptomic responses to allergen in airway epithelial cells"],"prefix":"10.1093","volume":"11","author":[{"given":"Anthony P","family":"Brown","sequence":"first","affiliation":[{"name":"California National Primate Research Center, University of California Davis , Davis, CA 95616,","place":["United 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National Primate Research Center, University of California Davis , Davis, CA 95616,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Pham","sequence":"additional","affiliation":[{"name":"California National Primate Research Center, University of California Davis , Davis, CA 95616,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1861-5316","authenticated-orcid":false,"given":"Artem","family":"Barski","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229,","place":["United States"]},{"name":"Division of Human Genetics, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229,","place":["United States"]},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine , Cincinnati, OH 45267,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew T","family":"Weirauch","sequence":"additional","affiliation":[{"name":"Center for Autoimmune Genomics and Etiology, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229,","place":["United States"]},{"name":"Division of Allergy and Immunology, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229,","place":["United States"]},{"name":"Division of Human Genetics, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229,","place":["United States"]},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine , Cincinnati, OH 45267,","place":["United States"]},{"name":"Division of Biomedical Informatics, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229,","place":["United States"]},{"name":"Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 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