title: FOXA1 plays a role in regulating secretoglobin 1a1 expression in the absence of CCAAT/enhancer binding protein activities in lung in vivo.
abstract: Secretoglobin (SCGB) 1A1, also called Clara cell secretor protein (CCSP) or Clara cell-specific 10-kDa protein (CC10), is a small molecular weight secreted protein mainly expressed in lung, with anti-inflammatory/immunomodulatory properties. Previous in vitro studies demonstrated that CCAAT/enhancer-binding proteins (C/EBPs) are the major transcription factors for the regulation of Scbg1a1 gene expression, whereas FOXA1 had a minimum effect on the transcription. To determine the in vivo role of C/EBPs in the regulation of SCGB1A1 expression, experiments were performed in which A-C/EBP, a dominant-negative form of C/EBP that interferes with DNA binding activities of all C/EBPs, was specifically expressed in lung. Surprisingly, despite the in vitro findings, expression of SCGB1A1 mRNA was not decreased in vivo in the absence of C/EBPs. This may be due to a compensatory role assumed by FOXA1 in the regulation of Scgb1a1 gene expression in lung in the absence of active C/EBPs. This disconnect between in vitro and in vivo results underscores the importance of studies using animal models to determine the role of specific transcription factors in the regulation of gene expression in intact multicellular complex organs such as lung.
authors.affiliation: Laboratory or Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Taketomo
authors.initials: T
authors.lastname: Kido
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tomita
authors.forename: Minoru
authors.initials: M
authors.lastname: Okamoto
authors.forename: Yan
authors.initials: Y
authors.lastname: Cai
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Charles
authors.initials: C
authors.lastname: Vinson
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Maru
authors.forename: Shioko
authors.initials: S
authors.lastname: Kimura
mesh_terms: D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004318:Doxycycline / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060765:Secretoglobins; D014162:Transfection; D014598:Uteroglobin / Q000235:genetics* / Q000378:metabolism
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C496500:Foxa1 protein, mouse; D051541:Hepatocyte Nuclear Factor 3-alpha; D011506:Proteins; D012333:RNA, Messenger; C556390:Scgb1a1 protein, mouse; C449818:Scgb3a2 protein, mouse; D060765:Secretoglobins; D004247:DNA; D014598:Uteroglobin; D008156:Luciferases; D004318:Doxycycline