Myxoid liposarcoma-associated EWSR1-DDIT3 selectively represses osteoblastic and chondrocytic transcription in multipotent mesenchymal cells.

PloS One
Kayo SuzukiTomoatsu Kimura

Abstract

Liposarcomas are the most common class of soft tissue sarcomas, and myxoid liposarcoma is the second most common liposarcoma. EWSR1-DDIT3 is a chimeric fusion protein generated by the myxoid liposarcoma-specific chromosomal translocation t(12;22)(q13;q12). Current studies indicate that multipotent mesenchymal cells are the origin of sarcomas. The mechanism whereby EWSR1-DDIT3 contributes to the phenotypic selection of target cells during oncogenic transformation remains to be elucidated. Reporter assays showed that the EWSR1-DDIT3 myxoid liposarcoma fusion protein, but not its wild-type counterparts EWSR1 and DDIT3, selectively repressed the transcriptional activity of cell lineage-specific marker genes in multipotent mesenchymal C3H10T1/2 cells. Specifically, the osteoblastic marker Opn promoter and chondrocytic marker Col11a2 promoter were repressed, while the adipocytic marker Ppar-γ2 promoter was not affected. Mutation analyses, transient ChIP assays, and treatment of cells with trichostatin A (a potent inhibitor of histone deacetylases) or 5-Aza-2'-deoxycytidine (a methylation-resistant cytosine homolog) revealed the possible molecular mechanisms underlying the above-mentioned selective transcriptional repression. The firs...Continue Reading

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Citations

Dec 19, 2015·Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons·Adepitan A OwoshoCherry L Estilo
Jun 9, 2016·Laboratory Investigation; a Journal of Technical Methods and Pathology·Marieke A de GraaffNeeta Somaiah
Nov 29, 2017·Oncology Letters·Kayo SuzukiTomoatsu Kimura
Jan 12, 2021·The Journal of Pathology·Sarmishta KannanKevin B Jones

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Methods Mentioned

BETA
transfection
immunoprecipitation
ChIP
PCR
acetylation
histone
acetylation or
Assay
X-ray

Software Mentioned

ImageJ
Excel

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