title: POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes.
abstract: In the process of seeking novel lung host defense regulators by analyzing genome-wide RNA sequence data from normal human airway epithelium, we detected expression of POU domain class 2-associating factor 1 (POU2AF1), a known transcription cofactor previously thought to be expressed only in lymphocytes. Lymphocyte contamination of human airway epithelial samples obtained by bronchoscopy and brushing was excluded by immunohistochemistry staining, the observation of upregulation of POU2AF1 in purified airway basal stem/progenitor cells undergoing differentiation, and analysis of differentiating single basal cell clones. Lentivirus-mediated upregulation of POU2AF1 in airway basal cells induced upregulation of host defense genes, including MX1, IFIT3, IFITM, and known POU2AF1 downstream genes HLA-DRA, ID2, ID3, IL6, and BCL6. Interestingly, expression of these genes paralleled changes of POU2AF1 expression during airway epithelium differentiation in vitro, suggesting POU2AF1 helps to maintain a host defense tone even in pathogen-free condition. Cigarette smoke, a known risk factor for airway infection, suppressed POU2AF1 expression both in vivo in humans and in vitro in human airway epithelial cultures, accompanied by deregulation of POU2AF1 downstream genes. Finally, enhancing POU2AF1 expression in human airway epithelium attenuated the suppression of host defense genes by smoking. Together, these findings suggest a novel function of POU2AF1 as a potential regulator of host defense genes in the human airway epithelium.
authors.affiliation: Department of Respiratory Medicine, West China Hospital, Sichuan University, Sichuan 610041, China; Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065;
authors.forename: Haixia
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065;
authors.forename: Angelika
authors.initials: A
authors.lastname: Brekman
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065;
authors.forename: Wu-Lin
authors.initials: WL
authors.lastname: Zuo
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065;
authors.forename: Xuemei
authors.initials: X
authors.lastname: Ou
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065;
authors.forename: Renat
authors.initials: R
authors.lastname: Shaykhiev
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065;
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Agosto-Perez
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065;
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065;
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Walters
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065;
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Salit
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065;
authors.forename: Yael
authors.initials: Y
authors.lastname: Strulovici-Barel
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065;
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Staudt
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medical College, New York, NY 10065; and.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kaner
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065; Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, NY 14853.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Mezey
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medical College, New York, NY 10065; and geneticmedicine@med.cornell.edu.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065;
authors.forename: Guoqing
authors.initials: G
authors.lastname: Wang
mesh_terms: D002454:Cell Differentiation; D016000:Cluster Analysis; D004847:Epithelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007109:Immunity / Q000235:genetics*; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*
chemical_list: C091546:POU2AF1 protein, human; D015534:Trans-Activators