A NEW MOUSE GENE, SRG3, RELATED TO THE SWI3 OF SACCHAROMYCES-CEREVISIAE, IS REQUIRED FOR APOPTOSIS INDUCED BY GLUCOCORTICOIDS IN A THYMOMA CELL-LINE

We isolated a new mouse gene that is highly expressed in thymocytes, t estis, and brain. This gene, SRG3, showed a significant sequence homol ogy to SWI3, a yeast transcriptional activator, and its human homolog BAF155. SRG3 encodes 1,100 amino acids and has 33-47% identity with SW I3 protein over three regions. The SRG3 protein contains an acidic NH, terminus, a myb-like DNA binding domain, a leucine-zipper motif, and a proline- and glutamine-rich region at its COOH terminus. Rabbit anti serum raised against a COOH-terminal polypeptide of the SRG3 recognize d a protein with an apparent molecular mass of 155 kD. The serum also detected a 170-kD protein that seems to be a mouse homologue of human BAF170. Immuno-precipitation of cell extract with the antiserum agains t the mouse SRG3 also brought down a 195-kD protein that could be reco gnized by an antiserum raised against human SWI2 protein. The results suggest that the SRG3 protein associates with a mouse SWI2. The SRG3 p rotein is expressed about three times higher in thymocytes than in per ipheral lymphocytes. The expression of anti-sense RNA to SRG3 mRNA in a thymoma cell line, S49.1, reduced the expression level of the SRG3 p rotein, and decreased the apoptotic cell death induced by glucocortico ids. These results suggest that the SRG3 protein is involved in the gl ucocorticoid-induced apoptosis in the thymoma cell line. This implicat es that the SRG3 may play an important regulatory role during T cell d evelopment in thymus.