title: Phosphorylated C/EBPβ influences a complex network involving YY1 and USF2 in lung epithelial cells.
abstract: The promoter of the cystic fibrosis transmembrane conductance regulator gene CFTR is tightly controlled by regulators including CCAAT/enhancer binding proteins (C/EBPs). We previously reported that the transcription factors YY1 and USF2 affect CFTR expression. We can now demonstrate that C/EBPβ, a member of the CCAAT family, binds to the CFTR promoter and contributes to its transcriptional activity. Our data reveal that C/EBPβ cooperates with USF2 and acts antagonistically to YY1 in the control of CFTR expression. Interestingly, YY1, a strong repressor, fails to repress the CFTR activation induced by USF2 through DNA binding competition. Collectively, the data strongly suggest a model by which USF2 functionally interacts with YY1 blocking its inhibitory activity, in favour of C/EBPβ transactivation. Further investigation into the interactions between these three proteins revealed that phosphorylation of C/EBPβ influences the DNA occupancy of YY1 and favours the interaction between USF2 and YY1. This phosphorylation process has several implications in the CFTR transcriptional process, thus evoking an additional layer of complexity to the mechanisms influencing CFTR gene regulation.
authors.affiliation: UFR de Médecine, Université Montpellier1, Montpellier, France ; INSERM U827, Laboratoire de Génétique de Maladies Rares, Montpellier, France.
authors.forename: Victoria
authors.initials: V
authors.lastname: Viart
authors.forename: Jessica
authors.initials: J
authors.lastname: Varilh
authors.forename: Estelle
authors.initials: E
authors.lastname: Lopez
authors.forename: Céline
authors.initials: C
authors.lastname: René
authors.forename: Mireille
authors.initials: M
authors.lastname: Claustres
authors.forename: Magali
authors.initials: M
authors.lastname: Taulan-Cadars
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D051720:Upstream Stimulatory Factors / Q000235:genetics / Q000378:metabolism*; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; C545012:CEBPB protein, human; C505032:CFTR protein, human; C497184:USF2 protein, human; D051720:Upstream Stimulatory Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D008156:Luciferases
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