Bidirectionality and transcriptional activity of the EWSR1 promoter region

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

Animals

Apoptosis Regulatory Proteins

Base Sequence

Bone Neoplasms

Calmodulin-Binding Proteins

Conserved Sequence

Gene Expression Regulation

Humans

Molecular Sequence Data

Neoplasm Proteins

Promoter Regions, Genetic

RNA-Binding Proteins

Reverse Transcriptase Polymerase Chain Reaction

Sarcoma, Ewing

Sequence Homology, Nucleic Acid

Transcription, Genetic

Transfection

Journal Article

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

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)