Functional domains of the SYT and SYT-SSX synovial sarcoma translocation proteins and co-localization with the SNF protein BRM in the nucleus

The t(X;18)(p11.2;q11.2) chromosomal translocation commonly found in synovi al sarcomas fuses the SM gene on chromosome 18 to either of two similar gen es, SSX1 or SSX2, on the X chromosome. The SYT protein appears to act as a transcriptional co-activator and the SSX proteins as cc-repressors, Here we have investigated the functional domains of the proteins. The SYT protein has a novel conserved 54 amino acid domain at the N-terminus of the protein (the SNH domain) which is found in proteins from a wide variety of species , and a C-terminal domain, rich in glutamine, proline, glycine and tyrosine (the QPGY domain), which contains the transcriptional activator sequences, Deletion of the SNH domain results in a more active transcriptional activa tor, suggesting that this domain acts as an inhibitor of the activation dom ain, The C-terminal SSX domain present in SYT-SSX translocation protein con tributes a transcriptional repressor domain to the protein. Thus, the fusio n protein has transcriptional activating and repressing domains. We demonst rate that the human homologue of the SNF2/Brahama protein BRM co-localizes with SYT and SYT-SSX in nuclear speckles, and also interacts with SYT and S YT-SSX proteins in vitro, This interaction may provide an explanation of ho w the SM protein activates gene transcription.