title: Epigenetic regulation of the IL-13-induced human eotaxin-3 gene by CREB-binding protein-mediated histone 3 acetylation.
abstract: The etiology of a variety of chronic inflammatory disorders has been attributed to the interaction of genetic and environmental factors. Herein, we identified a link between epigenetic regulation and IL-13-driven eotaxin-3 in the pathogenesis of chronic allergic inflammation. We first demonstrated that the cAMP-responsive element (CRE) site in the eotaxin-3 promoter affects IL-13-induced eotaxin-3 promoter activity. Furthermore, the CRE-binding protein-binding protein (CBP), a histone acetyltransferase, induced base-line and IL-13-induced eotaxin-3 promoter activity. Additionally, IL-13 treatment promoted global histone 3 acetylation as well as the formation of a complex containing CBP and STAT6 and the subsequent acetylation of histone 3 at the eotaxin-3 promoter. CBP gene silencing decreased IL-13-induced transcription of eotaxin-3. Conversely, inhibition of histone deacetylation increased IL-13-induced eotaxin-3 production. Clinical studies demonstrated markedly increased global acetylation of histone 3 in the inflamed tissue of patients with allergic inflammation. Collectively, these results identify an epigenetic mechanism involving CBP and chromatin remodeling in regulating IL-13-induced chemokine transcription.
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Lim
authors.forename: Thomas X
authors.initials: TX
authors.lastname: Lu
authors.forename: Carine
authors.initials: C
authors.lastname: Blanchard
authors.forename: Marc E
authors.initials: ME
authors.lastname: Rothenberg
mesh_terms: D000107:Acetylation; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000096:biosynthesis*; D044127:Epigenesis, Genetic / Q000502:physiology*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology*; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D006657:Histones; D018793:Interleukin-13; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D050882:CREB-Binding Protein; C494363:CREBBP protein, human