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Here, we show that the transcription factor, Kr\u00fcppel-like factor 15 (KLF15), is directly induced by glucocorticoids in primary human ASM, and that KLF15 represses ASM hypertrophy. We integrated transcriptome data from KLF15 overexpression with genome-wide analysis of RNA polymerase (RNAP) II and glucocorticoid receptor (GR) occupancy to identify phospholipase C delta 1 as both a KLF15-regulated gene and a novel repressor of ASM hypertrophy. Our chromatin immunoprecipitation sequencing data also allowed us to establish numerous direct transcriptional targets of GR in ASM. Genes with inducible GR occupancy and putative antiinflammatory properties included IRS2, APPL2, RAMP1, and MFGE8. Surprisingly, we also observed GR occupancy in the absence of supplemental ligand, including robust GR binding peaks within the IL11 and LIF loci. Detection of antibody\u2013GR complexes at these areas was abrogated by dexamethasone treatment in association with reduced RNA polymerase II occupancy, suggesting that noncanonical pathways contribute to cytokine repression by glucocorticoids in ASM. Through defining GR interactions with chromatin on a genome-wide basis in ASM, our data also provide an important resource for future studies of GR in this therapeutically relevant cell type.<\/jats:p>","DOI":"10.1165\/rcmb.2016-0357oc","type":"journal-article","created":{"date-parts":[[2017,4,4]],"date-time":"2017-04-04T16:39:29Z","timestamp":1491323969000},"page":"226-237","source":"Crossref","is-referenced-by-count":31,"title":["Glucocorticoid Receptor ChIP-Seq Identifies PLCD1 as a KLF15 Target that Represses Airway Smooth Muscle Hypertrophy"],"prefix":"10.1093","volume":"57","author":[{"given":"Sarah K.","family":"Sasse","sequence":"first","affiliation":[{"name":"Department of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vineela","family":"Kadiyala","sequence":"additional","affiliation":[{"name":"Department of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Danhorn","sequence":"additional","affiliation":[{"name":"Center for Genes, Health, and the Environment, National Jewish Health, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Reynold A.","family":"Panettieri","sequence":"additional","affiliation":[{"name":"Rutgers Institute for Translational Medicine and Science, Rutgers University, New Brunswick, New Jersey; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu L.","family":"Phang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony N.","family":"Gerber","sequence":"additional","affiliation":[{"name":"Department of Medicine and"},{"name":"Department of Medicine, University of Colorado, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,8,1]]},"reference":[{"key":"2026021122455684000_bib1","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1152\/japplphysiol.00950.2012","article-title":"Airway smooth muscle in the pathophysiology and treatment of asthma","volume":"114","author":"Doeing","year":"2013","journal-title":"J Appl Physiol (1985)"},{"key":"2026021122455684000_bib2","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.ccm.2012.05.002","article-title":"Airway smooth muscle in asthma: just a target for bronchodilation?","volume":"33","author":"Black","year":"2012","journal-title":"Clin Chest Med"},{"key":"2026021122455684000_bib3","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.pharmthera.2016.04.002","article-title":"Bronchoprotection and bronchorelaxation in asthma: new targets, and new ways to target the old ones","volume":"164","author":"Pera","year":"2016","journal-title":"Pharmacol Ther"},{"key":"2026021122455684000_bib4","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1378\/chest.07-0262","article-title":"Is airway smooth muscle the \u201cmissing link\u201d modulating airway inflammation in asthma?","volume":"133","author":"Tliba","year":"2008","journal-title":"Chest"},{"key":"2026021122455684000_bib5","doi-asserted-by":"crossref","first-page":"L912","DOI":"10.1152\/ajplung.00259.2013","article-title":"Airway smooth muscle in airway reactivity and remodeling: what have we learned?","volume":"305","author":"Prakash","year":"2013","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026021122455684000_bib6","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.jaci.2011.06.002","article-title":"What effect does asthma treatment have on airway remodeling? 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