IDENTIFICATION OF A CANDIDATE C-MOS REPRESSOR THAT RESTRICTS TRANSCRIPTION OF GERM CELL-SPECIFIC GENES

The c-mos proto-oncogene is specifically expressed in female and male germ cells. Previous studies identified a negative regulatory element (NRE) upstream of the c-mos promoter that suppresses c-mos transcripti on in transfected NIH 3T3 cells. In this study, we used gel shift assa ys to detect proteins in nuclear extracts of NIH 3T3 cells that bind t o the c-mos NRE in a sequence-specific manner. One protein was found t o bind to a region of the NRE which was shown by site-directed mutagen esis to be required for suppression of c-mos transcription. This facto r was present in nuclear extracts of several somatic cell lines and ti ssues but not in male germ cells in which c-mos is transcribed, sugges ting that it is a somatic cell repressor of c-mos transcription, The b inding site of the candidate repressor within the c-mos NRE consists o f sequences related to putative NREs identified in two other male germ cell-specific genes (encoding protamine 2 and phosphoglycerate kinase 2). The c-mos repressor bound and could be ITV cross-linked to these protamine 2 and phosphoglycerate kinase 2 gene sequences as a protein with an apparent molecular mass of similar to 30 kDa, The repressor bi nding site is also conserved in two other germ cell-specific genes (en coding testis-specific cytochrome c and heat shock-like protein 70), s uggesting that the c-mos repressor may be generally involved in suppre ssing transcription of germ cell-specific genes in somatic cells.