SYT associates with human SNF/SWI complexes and the C-terminal region of its fusion partner SSX1 targets histones.
A global transcriptional co-activator, the SNF/SWI complex, has been characterized as a chromatin remodeling factor that enhances accessibility of the transcriptional machinery to DNA within a repressive chromatin structure. On the other hand, mutations in some human SNF/SWI complex components have been linked to tumor formation. We show here that SYT, a partner protein generating the synovial sarcoma fusion protein SYT-SSX, associates with native human SNF/SWI complexes. The SYT protein has a unique QPGY domain, which is also present in the largest subunits, p250 and the newly identified homolog p250R, of the corresponding SNF/SWI complexes. The C-terminal region (amino acids 310-387) of SSX1, comprising the SSX1 portion of the SYT-SSX1 fusion protein, binds strongly to core histones and oligonucleosomes in vitro and directs nuclear localization of a green fluorescence protein fusion protein. Experiments with serial C-terminal deletion mutants of SSX1 indicate that these properties map to a common region and also correlate with the previously demonstrated anchorage-independent colony formation activity of SYT-SSX in Rat 3Y1 cells. These data suggest that SYT-SSX interferes with the function of either the SNF/SWI complexes or another SYT-interacting co-activator, p300, by changing their targeted localization or by directly inhibiting their chromatin remodeling activities.
Pubmed ID: 11734557 RIS Download
Amino Acid Sequence | Cell Line | Cell Nucleus | Chromatin | Electrophoresis, Polyacrylamide Gel | Gene Deletion | Glutathione Transferase | HeLa Cells | Histones | Humans | Immunoblotting | Models, Genetic | Molecular Sequence Data | Mutagenesis, Site-Directed | Plasmids | Protein Binding | Protein Structure, Tertiary | Protein-Serine-Threonine Kinases | Proteins | Proto-Oncogene Proteins | Recombinant Fusion Proteins | Repressor Proteins | Transcription Factors | Transcription, Genetic