Bidirectionality and transcriptional activity of the EWSR1 promoter region

TY - JOUR

T1 - Bidirectionality and transcriptional activity of the EWSR1 promoter region

AU - Möller, Emely

AU - Mandahl, Nils

AU - Iliszko, Mariola

AU - Mertens, Fredrik

AU - Panagopoulos, Ioannis

PY - 2009/3

Y1 - 2009/3

N2 - 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.

AB - 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.

KW - Animals

KW - Apoptosis Regulatory Proteins

KW - Base Sequence

KW - Bone Neoplasms

KW - Calmodulin-Binding Proteins

KW - Conserved Sequence

KW - Gene Expression Regulation

KW - Humans

KW - Molecular Sequence Data

KW - Neoplasm Proteins

KW - Promoter Regions, Genetic

KW - RNA-Binding Proteins

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Sarcoma, Ewing

KW - Sequence Homology, Nucleic Acid

KW - Transcription, Genetic

KW - Transfection

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.3892/or_00000267

DO - 10.3892/or_00000267

M3 - Article

C2 - 19212622

VL - 21

SP - 641

EP - 648

JO - Oncology Reports

JF - Oncology Reports

SN - 1791-2431

IS - 3

ER -