title: NFAT-1, Sp-1, Sp-3, and miR-21: New regulators of chemokine C receptor 7 expression in mature human dendritic cells.
abstract: The chemokine C receptor 7 (CCR7) is a G-protein-coupled heptahelical receptor (GPCR) that is expressed on a wide variety of cells including memory T cells, B cells, mature dendritic cells, and cancer cells. Activated by its ligands CCL19 or CCL21, CCR7 plays a major role in metastasis of cancer cells. Recent studies demonstrated the role of NF-κB and AP-1 transcription factors in addition to let-7 microRNA in CCR7 expression. Our ChIP assays further show the binding of Sp-1, Sp-3 and NFAT-1 transcription factors to their potential binding sites in the 1Kb promoter region with the later found to inhibit whilst Sp-1, and Sp-3 were found to stimulate CCR7 expression as demonstrated by transfection assays. On the other hand, in addition to the known let-7 regulation of CCR7, we found miR-21 to have a highly conserved target region in CCR7 3'UTR and to be significantly down-regulated during the course of dendritic cell maturation, allowing for high expression of CCR7.
authors: Department of Biochemistry, Laboratory of Immunology, EDST-PRASE, Lebanese University, Faculty of Sciences, Hadath-Beirut, Lebanon.
authors: Carine
authors: C
authors: Al Akoum
authors: Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, 121, Boulevard de Waterloo, 1000 Bruxelles, Belgium.
authors: Israa
authors: I
authors: Akl
authors: Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, 121, Boulevard de Waterloo, 1000 Bruxelles, Belgium.
authors: Redouane
authors: R
authors: Rouas
authors: Department of Biochemistry, Laboratory of Immunology, EDST-PRASE, Lebanese University, Faculty of Sciences, Hadath-Beirut, Lebanon.
authors: Mohammad
authors: M
authors: Fayyad-Kazan
authors: Department of Biochemistry, Laboratory of Immunology, EDST-PRASE, Lebanese University, Faculty of Sciences, Hadath-Beirut, Lebanon.
authors: Layal
authors: L
authors: Falha
authors: Innate Immune Signalling and Oncogenesis Group Lyon Cancer Research Center, Centre Léon Bérard, 28 rue Laennec, 69373 Lyon, France.
authors: Toufic
authors: T
authors: Renno
authors: Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, 121, Boulevard de Waterloo, 1000 Bruxelles, Belgium.
authors: Arsène
authors: A
authors: Burny
authors: Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, 121, Boulevard de Waterloo, 1000 Bruxelles, Belgium.
authors: Philippe
authors: P
authors: Lewalle
authors: Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, 121, Boulevard de Waterloo, 1000 Bruxelles, Belgium.
authors: Hussein
authors: H
authors: Fayyad-Kazan
authors: Department of Biochemistry, Laboratory of Immunology, EDST-PRASE, Lebanese University, Faculty of Sciences, Hadath-Beirut, Lebanon. Electronic address: bassam.badran@ul.edu.lb.
authors: Bassam
authors: B
authors: Badran
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051705:Sp3 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C515370:CCR7 protein, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D050778:NFATC Transcription Factors; D054400:Receptors, CCR7; C497121:SP3 protein, human; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; C487931:mirnlet7 microRNA, human; D051705:Sp3 Transcription Factor
keywords: CCR7; Dendritic cells; Maturation; MicroRNA; Promoter