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To date, genetic factors associated with asthma susceptibility have been unable to explain the full etiology of asthma. Recent studies have demonstrated that the epigenetic disruption of gene expression plays an equally important role in the development of asthma through interaction with our environment. We sensitized 6\u2010week\u2010old C57BL\/6J mice with house\u2010dust\u2010mite (HDM) extracts intraperitoneally followed by 5 weeks of exposure to HDM challenges (three times a week) intratracheally. HDM\u2010exposed mice showed an increase in airway hyper\u2010responsiveness (AHR) and inflammation together with structural remodeling of the airways. We applied methylated DNA immunoprecipitation\u2010next generation sequencing (MeDIP\u2010seq) for profiling of DNA methylation changes in the lungs in response to HDM. We observed about 20 million reads by a single\u2010run of massive parallel sequencing. We performed bioinformatics and pathway analysis on the raw sequencing data to identify differentially methylated candidate genes in HDM\u2010exposed mice. Specifically, we have revealed that the transforming growth factor beta signaling pathway is epigenetically modulated by chronic exposure to HDM. Here, we demonstrated that a specific allergen may play a role in AHR through an epigenetic mechanism by disrupting the expression of genes in lungs that might be involved in airway inflammation and remodeling. Our findings provide new insights into the potential mechanisms by which environmental allergens induce allergic asthma and such insights may assist in the development of novel preventive and therapeutic options for this debilitative disease. Environ. Mol. Mutagen. 55:244\u2013255, 2014. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/em.21851","type":"journal-article","created":{"date-parts":[[2014,1,21]],"date-time":"2014-01-21T05:43:11Z","timestamp":1390282991000},"page":"244-255","source":"Crossref","is-referenced-by-count":43,"title":["Alterations of the lung methylome in allergic airway hyper\u2010responsiveness"],"prefix":"10.1002","volume":"55","author":[{"given":"Robert YS","family":"Cheng","sequence":"first","affiliation":[{"name":"Radiation Biology Branch National Cancer Institute National Institutes of Health Bethesda Maryland United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences Johns Hopkins Bloomberg School of Public Health Baltimore Maryland United States"},{"name":"Department of Respiratory Diseases Changhai Hospital, Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathachit","family":"Limjunyawong","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences Johns Hopkins Bloomberg School of Public Health Baltimore Maryland United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyna","family":"Dao","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences Johns Hopkins Bloomberg School of Public Health Baltimore Maryland United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandhya","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences Johns Hopkins Bloomberg School of Public Health Baltimore Maryland United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Rabold","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences Johns Hopkins Bloomberg School of Public Health Baltimore Maryland United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James SK","family":"Sham","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore Maryland United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne","family":"Mitzner","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences Johns Hopkins Bloomberg School of Public Health Baltimore Maryland United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan\u2010Yee","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences Johns Hopkins Bloomberg School of Public Health Baltimore Maryland United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,1,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1843.2011.01974.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.09.034"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/23.2.335"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1513\/pats.200705-063VS"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20403"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009674"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.12.963"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200901-0135OC"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.088773.108"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.10.6384"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63371-8"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2012.07.002"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.5.285"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1995.79.2.560"},{"key":"e_1_2_7_16_1","unstructured":"FerreiraMA MathesonMC DuffyDL MarksGB HuiJ LeSou\u00ebfP DanoyP BalticS NyholtDR JenkinsM et al; Australian Asthma Genetics Consortium.2011. 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