Potential antagonism of polycomb silencing by the SYTSSX oncogene Free

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Synovial sarcoma is a soft tissue cancer that typically afflicts young adults. In about 90% of cases, this disease associated with a chromosomal translocation between the SYT gene (chromosome 18) and the SSX gene (chromosome X). This results in the formation of a fusion protein named SYTSSX. Little is known about the role that SYTSSX plays in synovial sarcoma development. Studies by our group and others have demonstrated an interaction between SYT, SYTSSX and chromatin remodeling complexes. These chromatin modifying machineries include the ATP-dependent SWI/SNF chromatin remodeling complex as well as the acetyltransferase p300. SWI/SNF complexes and p300 are usually associated with the facilitation of gene activation. Interestingly, SYTSSX can specifically target both SWI/SNF complexes and p300 to regions of transcription repression called polycomb bodies. Polycomb bodies are aggregates of transcriptional repressors called polycomb complexes, which function in the regulation of numerous developmental processes. Recruitment of p300, SWI/SNF complexes and other modifers may antagonize normal polycomb function and lead to the reexpression of polycomb target genes. Consistent with this hypothesis, increases in histone acetylation, a marker for transcriptionally permissive chromatin, are observed in the polycomb bodies of SYTSSX-expressing cells, but not controls. Interestingly, SYTSSX appears to cause a loss of immunoreactivity of the polycomb complex protein Bmi1 to a Bmi1-specific antibody on immunoblots. This phenomenon does not appear to be due to changes in the transcription, protein stability or extractability of Bmi1 from chromatin. This loss of signal might result from epitope masking through a post-translational modification. Evidence suggests that hyperphosphorylation of Bmi1 in the presence of SYTSSX may cause this loss of signal. We propose that this decrease in Bmi1 immunoreactivity is a mechanism by which SYTSSX modulates polycomb silencing.