title: Identification and functional characterization of the human and murine fibroblast growth factor receptor 4 promoters.
abstract: Fibroblast growth factor receptors (FGFRs) play crucial roles in signal transduction of adult tissues and during embryonic development. To study the transcriptional control, we isolated and characterized the promoter of human FGFR4. Two transcription initiation sites were identified. The deletion analysis in different cell types defined a core promoter reaching from -9 to -198, lacking TATA and CCAAT boxes but displaying high GC content (77%) in a stretch of 300 bp upstream of the major mRNA start. This region harbors multiple binding motifs for transcription factors. Moreover, the region between -1085 and -1140 contains a potential repressor element, which downregulates transcriptional activity. To identify conserved regulatory elements, we isolated and analyzed also the murine FGFR4 promoter. Only one transcription start was identified using RNase protection assays. Sequence alignment of human and mouse shows a striking similarity in the core promoter region of both genes, encompassing conserved transcription factor binding sites and a splice acceptor site. Furthermore, the region containing the putative repressor element is also conserved suggesting a functional role for gene expression.
authors.affiliation: Department of Obstetrics and Gynecology, Department of Pathology, School of Medicine, J. W. Goethe-University, Theodor-Stern-Kai 7, Frankfurt, 60590, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Becker
authors.forename: A
authors.initials: A
authors.lastname: Bräuninger
authors.forename: G
authors.initials: G
authors.lastname: Wolf
authors.forename: M
authors.initials: M
authors.lastname: Kaufmann
authors.forename: K
authors.initials: K
authors.lastname: Strebhardt
mesh_terms: D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000032:analysis; D005091:Exons; D005786:Gene Expression Regulation; D016678:Genome; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D051499:Receptor, Fibroblast Growth Factor, Type 4; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D004247:DNA; C496371:FGFR4 protein, human; C496372:Fgfr4 protein, mouse; D051499:Receptor, Fibroblast Growth Factor, Type 4