A Gene-Specific Promoter in Transgenic Mice Directs Testis-Specific Demethylation Prior to Transcriptional Activation In Vivo

Transcription of the autosomal phosphoglycerate kinase gene, Pgk-2, is initiated at the onset of meiosis during spermatogenesis in mammals. However, in the mouse, the 5ʹ portion of the endogenous Pgk-2 coding sequence undergoes a specific demethylation event that precedes transcriptional activation by 10-12 days. Here we show that transgenes consisting of the Pgk-2 core promoter ligated to the CAT reporter gene undergo a similar tissue-, stage-, and cell type-specific demethylation in the 5ʹ portion of the CAT coding sequence, whereas transgenes consisting of the CAT reporter sequence alone, or of the CAT sequence ligated to the CpG islandcontaining transferrin gene promoter, demonstrate different patterns of demethylation. These results indicate that specific promoter sequences can influence the pattern of tissue-specific demethylation within different genes and that a signal for spermatogenic cellspecific demethylation resides within the core promoter of the mammalian Pgk-2 gene.