title: Bidirectionality and transcriptional activity of the EWSR1 promoter region.
abstract: EWSR1 is involved in chimeric proteins which play crucial roles in the development of a variety of bone and soft tissue tumors. Many of the chimeric genes involving EWSR1 have been extensively studied, whereas less is known about the wild-type (wt) gene and its regulation. As the expression of the chimeric gene is driven by the EWSR1 promoter, it is of importance to study the mechanisms regulating wt EWSR1 expression. We estimated the transcriptional activity of the EWSR1 promoter through deletion fragments driving reporter gene expression. This assay identified the 100-bp region immediately downstream of the EWSR1 transcriptional start site (+1) and the downstream region from +100 to +300 as important regions for transcriptional regulation. We also found that EWSR1 and RHBDD3, a gene located directly upstream of EWSR1 that is likely to share regulatory elements with EWSR1, were co-expressed in the tissue panels, Ewing tumor biopsies and cell lines. Thus, our results show that the EWSR1 promoter functions in a bidirectional manner, thereby regulating also RHBDD3, and identifies specific regions that strongly influence promoter activity.
authors.affiliation: Department of Clinical Genetics, Lund University Hospital, SE-221 85 Lund, Sweden. emely.moller@med.lu.se
authors.forename: Emely
authors.initials: E
authors.lastname: Möller
authors.forename: Nils
authors.initials: N
authors.lastname: Mandahl
authors.forename: Mariola
authors.initials: M
authors.lastname: Iliszko
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
authors.forename: Ioannis
authors.initials: I
authors.lastname: Panagopoulos
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001483:Base Sequence; D001859:Bone Neoplasms / Q000235:genetics*; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D017124:Conserved Sequence; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012512:Sarcoma, Ewing / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection
chemical_list: D051017:Apoptosis Regulatory Proteins; D002148:Calmodulin-Binding Proteins; C500986:EWSR1 protein, human; D009363:Neoplasm Proteins; C496066:RHBDD3 protein, human; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins