Transcriptional regulation of spatiotemporal gene expression within the seminiferous epithelium: Mouse Acrv1 gene as a model

Precise spatiotemporal expression of cohorts of differentiation markers unique to spermatogonia, spermatocytes, and round spermatids punctuates spermatogenesis and ensures its completion. For example, genes coding for the synaptonemal complex or the acrosome or flagellum are expressed sequentially in a developmental stage- and germ cell-specific manner. But the transcriptional mechanisms governing the spatiotemporal order of gene expression within the seminiferous epithelium are poorly understood. Using the round spermatid-specific Acrv1 gene, which codes for the acrosomal protein SP-10 as a model, we learned that (1) the proximal promoter itself contains all the necessary cis-regulatory sequences, (2) an insulator prevents somatic cell expression of the testis-specific gene, (3) RNA II polymerase is loaded on the Acrv1 promoter but paused in spermatocytes, thus ensuring precise transcriptional elongation in round spermatids, and that (4) a transcriptional repressor binding protein of 43 kilodaltons (TDP-43) plays a role in maintaining the paused state in spermatocytes. Although the Acrv1 enhancer element has been narrowed down to 50 bp and its binding to a 47 kDa testis-abundant nuclear protein shown, the identity of the putative transcription factor responsible for activation of round spermatid-specific transcription remains elusive. Human male infertility is idiopathic with limited treatment options. Understanding transcriptional regulation of spermatogenesis has the potential to lead to future therapies for male infertility.