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 transcription in transfected NIH 3T3 cells. In this study, we used gel shift assays to detect proteins in nuclear extracts of NIH 3T3 cells that bind to the c-mos NRE in a sequence-specific manner. One protein was found to bind to a region of the NRE which was shown by site-directed mutagenesis to be required for suppression of c-mos transcription. This factor was present in nuclear extracts of several somatic cell lines and tissues but not in male germ cells in which c-mos is transcribed, suggesting that it is a somatic cell repressor of c-mos transcription. The binding site of the candidate repressor within the c-mos NRE consists of 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 UV cross-linked to these protamine 2 and phosphoglycerate kinase 2 gene sequences as a protein with an apparent molecular mass of approximately 30 kDa. The repressor binding site is also conserved in two other germ cell-specific genes (encoding testis-specific cytochrome c and heat shock-like protein 70), suggesting that the c-mos repressor may be generally involved in suppressing transcription of germ cell-specific genes in somatic cells.