Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.
Project description:We identified global DNA binding properties of EWS-FLI1 in mouse Ewing sarcoma. GGAA microsatellites were found as binding sites of EWS-FLI1 but with less frequency than that in human Ewing sarcoma, and genomic distribution is not conserved between human and mouse.
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.
Project description:Ewing sarcoma is an aggressive malignancy characterized by oncogenic rearrangements of the EWS gene with an ETS-family transcription factor, most commonly FLI. Recent comprehensive next-generation sequencing efforts have revealed few other highly recurrent mutations in this disease apart from loss-of-function mutations in STAG2 which occur in 15-20% of tumors. STAG2 is a member of the cohesin complex, which regulates sister chromatid alignment during mitosis and epigenetic regulation of gene expression. While some studies suggest that loss of STAG2 is associated with the development of aneuploidy, this is not the case in Ewing sarcoma. To investigate whether STAG2 loss affects epigenetic regulation of gene expression in Ewing sarcoma, we developed isogenic Ewing sarcoma cell lines with STAG2 knockout. We found that Ewing sarcoma cells engineered for loss of STAG2 maintain an intact cohesion complex that alternately incorporates STAG1.
