CAATT/enhancer-binding proteins alpha and delta interact with NKX2-1 to synergistically activate mouse secretoglobin 3A2 gene expression.
Secretoglobin (SCGB) 3A2 is a small molecular weight secreted protein predominantly expressed in lung airways. We previously demonstrated that the expression of SCGB3A2 is regulated by homeodomain transcription factor NKX2-1. Here we show that CCAAT/enhancer-binding proteins, C/EBPalpha and C/EBPdelta, regulate mouse Scgb3a2 gene transcription in vivo and in vitro by binding to specific sites located in the Scgb3a2 promoter and the activity is synergistically enhanced through cooperative interaction with NKX2-1. Six C/EBP binding sites lie within 500 bp of the Scgb3a2 gene promoter, of which two sites, located at -44 to -54 bp and -192 to -201 bp, appear to be critical for the synergistic activation of Scgb3a2 gene transcription with NKX2-1. All three transcription factors, C/EBPalpha, C/EBPdelta, and NKX2-1, are expressed in the epithelial cells of airways, particularly the bronchus, where high expression of SCGB3A2 is found. The expression of these transcription factors markedly increases toward the end of gestation, which coincides with the marked increase of SCGB3A2, suggesting the importance of C/EBPalpha and C/EBPdelta, and their synergistic interaction with NKX2-1 in mouse Scgb3a2 gene transcription and lung development.
Tomita
Takeshi
T
Laboratory of Metabolism, NCI, National Institutes of Health, Bethesda, Maryland 20892.
Kido
Taketomo
T
Laboratory of Metabolism, NCI, National Institutes of Health, Bethesda, Maryland 20892.
Kurotani
Reiko
R
Laboratory of Metabolism, NCI, National Institutes of Health, Bethesda, Maryland 20892; Cardiovascular Research Institute, Yokohama City University, Yokohama 236-0006, Japan.
Iemura
Shun-Ichiro
SI
National Institutes of Advanced Industrial Science and Technology, Biological Information Research Center, Tokyo 135-0064, Japan.
Sterneck
Esta
E
Laboratory of Cell and Developmental Signaling, NCI, Frederick, Maryland 21702-1201.
Natsume
Tohru
T
National Institutes of Advanced Industrial Science and Technology, Biological Information Research Center, Tokyo 135-0064, Japan.
Vinson
Charles
C
Laboratory of Metabolism, NCI, National Institutes of Health, Bethesda, Maryland 20892.
Kimura
Shioko
S
Laboratory of Metabolism, NCI, National Institutes of Health, Bethesda, Maryland 20892. Electronic address: kimuras@mail.nih.gov.
D000818:Animals; D001483:Base Sequence; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism*; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D008168:Lung / Q000196:embryology*; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D060765:Secretoglobins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism*
D022763:CCAAT-Enhancer-Binding Protein-alpha; D004268:DNA-Binding Proteins; C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D011506:Proteins; C449818:Scgb3a2 protein, mouse; D060765:Secretoglobins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta