Transcriptional control of the heme oxygenase gene during mouse spermatogenesis

The activation of the heme oxygenase (HO) gene during development of mouse male germ cells was examined by nuclear run-off assay. Results showed that the HO gene was activated in male germ cells, especially in spermatogonia and that the mRNA was stored throughout meiosis. In contrast, Western blotting analysis revealed that HO was expressed during spermatogenesis to spermatocytes. As the mouse HO gene is known to have a 12-o-tetradecanoyl-phorbol 13-acetate(TPA)-responsive element (TRE) in its upstream region and is activated by TPA in mouse M1 cells, we also examined the activation of the nuclear proto-oncogenes fos and jun, which are activators of TRE. Both genes were found to be activated with expression of their protein products only in spermatogonia. Moreover activation of fos, jun and HO genes in spermatogonia was strongly inhibited by a c-kinase inhibitor. These results suggest that the HO gene is activated at the spermatogonia stage by a fos/jun heterodimer complex (AP1) through c-kinase activation.