Transcription of the testis-specific gene is selectively activated in primary spermatocytes

Transcription of the testis-specific gene is selectively activated in primary spermatocytes to provide a source of phosphoglycerate kinase that is critical to normal motility and fertility of mammalian spermatozoa. transcription of the gene during spermatogenesis. We propose that binding of Bisoprolol manufacture PBX4, plus its coactivator PREP1, is a rate-limiting step leading to the initiation of tissue-specific transcription of the gene. This study provides insight into the developmentally dynamic establishment of tissue-specific protein-DNA interactions in vivo. It also allows us to speculate about the events that led to tissue-specific regulation of the gene during mammalian evolution. Spermatogenesis is usually a highly ordered process by which the germ cell lineage gives rise to functional gametes in the male. Development of Bisoprolol manufacture the spermatogenic lineage involves unique events, including meiosis and genetic recombination, as well as dramatic morphological changes during spermiogenesis that give rise to the uniquely structured spermatozoon (7). As with other specific lineages in mammalian organisms, the characteristic differentiation of male germ cells proceeds as a result of expression of unique combinations of genes (17). Recent studies have revealed that spermatogenic cells express a surprisingly large proportion Bisoprolol manufacture of genes in the murine genome. Microarray studies show that the majority of differential gene expression observed in the developing testis occurs in spermatogenic cells and that dynamic changes in gene expression accompany transitions from premeiotic to meiotic and from meiotic to postmeiotic stages of spermatogenesis (2, 52, 53). The same microarray studies have also confirmed that a large number of genes are expressed exclusively in spermatogenic cells. Thus, spermatogenesis is usually characterized by a unique transcriptome that undergoes dynamic, stage-specific changes, and this implies the ongoing function of mechanisms regulating tissue- and stage-specific transcription (37, 39). Among the many germ cell-specific genes expressed during spermatogenesis is a set encoding isozymes that function during glycolysis, primarily in spermatozoa. These include the genes, which encode sperm-specific isozymes of lactate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, hexokinase, phosphoglycerate mutase, pyruvate dehydrogenase E1 alpha, and phosphoglycerate kinase, respectively (13, 17, 20, 42). In mammals, two genes encode the glycolytic enzyme phosphoglycerate kinase, the X-linked gene and the autosomal gene (58). The gene is usually widely expressed in all somatic cells, oogenic cells, and premeiotic spermatogenic cells, whereas the gene is usually expressed exclusively in meiotic spermatocytes and postmeiotic spermatids, where expression of the gene is usually repressed by meiotic sex chromosome inactivation (MSCI) (57) and by the subsequent repressive effects of postmeiotic sex chromatin (PMSC) (38, 45, 60). The promoter of the gene is usually believed to have derived from that of the gene as part of a retroposition event that led to the genesis of the gene early during mammalian evolution (12, 40). Thus, although the promoter was Edem1 likely initially identical to the promoter, it appears to have diverged, especially in eutherian mammals, to facilitate tissue-specific expression. Evidence favoring a common ancestry of these two promoters includes the absence of a TATA box and the presence of GC and CAAT box elements in both (34, 35). Although this core promoter region from the gene is able to direct transcription of a downstream reporter gene in transient transfection assays (12), this portion alone is usually insufficient to direct expression of a reporter gene in vivo in transgenic mice (48). Indeed, a minimum of an additional 42 bp of enhancer sequence immediately upstream of the core promoter, along with the core promoter itself, is required to direct testis-specific expression in vivo (62). The acquisition of tissue-specific function at this enhancer region, along with the loss in the promoter of the CpG island present in the promoter, represents key differences that we previously suggested may have facilitated the evolution of testis-specific regulation of the gene (34, 35). We previously used a combination of analyses in vitro and in vivo to determine that spermatogenesis-specific expression of the gene is usually regulated by.