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Genomewide occupancy of the synovial sarcoma-associated SYT-SSX2 oncoprotein in C2C12 myoblasts

ABSTRACT: Synovial sarcoma is a rare malignancy that is characterized by the presence of a chromosomal translocation t(X;18). This genetic abnormality results in the fusion of 2 transcriptional co-regulators, SYT and SSX, which have been shown to mediate transcriptional activation and repression, respectively. Although the fusion protein does not bind DNA directly, SYT-SSX2 is known to function through interaction with chromatin-modifying complexes. In this study, we wanted to determine the SYT-SSX2 occupancy across the whole genome in order to further characterize its function by identifying genes that may be deregulated by this protein.

ORGANISM(S): Mus musculus

PROVIDER: GSE26564 | GEO | 2011/09/26

SECONDARY ACCESSION(S): PRJNA142109

REPOSITORIES: GEO

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Genomewide occupancy of the synovial sarcoma-associated SYT-SSX2 oncoprotein in C2C12 myoblasts

Project description:Synovial sarcoma is a rare malignancy that is characterized by the presence of a chromosomal translocation t(X;18). This genetic abnormality results in the fusion of 2 transcriptional co-regulators, SYT and SSX, which have been shown to mediate transcriptional activation and repression, respectively. Although the fusion protein does not bind DNA directly, SYT-SSX2 is known to function through interaction with chromatin-modifying complexes. In this study, we wanted to determine the SYT-SSX2 occupancy across the whole genome in order to further characterize its function by identifying genes that may be deregulated by this protein. C2C12 myoblasts were infected with retrovirus carrying SYT-SSX2-HA-FLAG expression vector. Chromatin immunoprecipitation (ChIP) was performed on cell lysates with either control IgG antibody (Abcam) or anti-FLAG antibody (Sigma). Lysates from 2 independent infections were pooled and used to isolate control ChIP DNA (IgG). DNA from 2 independent FLAG ChIP experiments (each using lysates from 2 independent infections) was pooled for SYT-SSX2 ChIP.

2011-09-26 | E-GEOD-26564 | biostudies-arrayexpress

Gene expression profile of SYT-SSX2-expressing C2C12 myoblasts

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Gene expression profile of SYT-SSX2-expressing C2C12 myoblasts

Project description:Synovial sarcoma is a rare malignancy characterized by the presence of a specific chromosomal translocation t(X;18) that results in the formation of a fusion protein SYT-SSX. Because it is believed that synovial sarcoma arises from mesenchymal stem or progenitor cells, we wanted to determine the changes in gene expression caused by SYT-SSX2 in untransformed mesenchymal progenitor cells - murine C2C12 myoblasts in this experiment. In 2 independent experiments, C2C12 myoblasts were infected with retrovirus carrying either control vector (pOZ) or SYT-SSX2 expression vector. Total cellular RNA was extracted 48 hours post-infection and utilized for microarray analysis on Affymetrix arrays.

2011-09-25 | E-GEOD-26562 | biostudies-arrayexpress

Reprogramming of mesenchymal stem cells by the synovial sarcoma-associated oncogene SYT-SSX2

Project description:Cellular identity is determined by its gene expression programs. The ability of the cell to change its identity and produce cell types outside its lineage is achieved by the activity of transcription controllers capable of reprogramming differentiation gene networks. The synovial sarcoma associated protein, SYT-SSX2, reprograms myogenic progenitors and human bone marrow-derived mesenchymal stem cells (BMMSCs) by dictating their commitment to a pro-neural lineage. It fulfills this function by directly targeting an extensive array of neural-specific genes as well as genes of developmental pathway mediators. Concomitantly, the ability of both myoblasts and BMMSCs to differentiate into their normal myogenic and adipogenic lineages was compromised. Synovial sarcoma is believed to arise in mesenchymal stem cells where formation of the t(X;18) translocation product, SYT-SSX, constitutes the primary event in the cancer. SYT-SSX is therefore believed to initiate tumorigenesis in its target stem cell. The data presented here allow a glimpse at the initial events that likely occur when SYT-SSX2 is first expressed and its dominant function in subverting the nuclear program of the stem cell, leading to its aberrant differentiation, as a first step toward transformation. In addition, we identified the fibroblast growth factor receptor gene, Fgfr2, as one occupied and upregulated by SYT-SSX2. Knockdown of FGFR2 in both BMMSCs and synovial sarcoma cells abrogated their growth and attenuated their neural phenotype. These results support the notion that the SYT-SSX2 nuclear function and differentiation effects are conserved throughout sarcoma development and are required for its maintenance beyond the initial phase. They also provide the stem cell regulator, FGFR2 as a promising candidate target for future synovial sarcoma therapy. This SuperSeries is composed of the SubSeries listed below.

2011-09-26 | GSE26565 | GEO

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Project description:We established human pluripotent stem cell (PSC) lines expressing Synovial Sarcoma-specific oncogene, SYT-SSX2, under the control of doxycycline with dose- and time-dependent manner. Gene expression profiles were analyzed to identify early response genes of SYT-SSX2. SYT-SSX2-inducible PSC lines including two hESCs and one hiPSC were analyzed at several time points (0, 6, 12, 18, 24 hours) after doxycycline treatment.

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SYT-SSX murine synovial sarcoma model

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