The Bivalent Chromatin and a Potential Silencer for Differential Expression of <i>PRSS</i> Genes in the Human Testis

The gene regulatory mechanism of individual genes during spermatogenesis is well understood in model animals, but not in non-model animals such as human. The mouse Prss/Tessp locus encompassing six testis-specific protease genes is a model of gene function and regulation in the testis. Here we investigated the expression and regulation of PRSS locus in primates, especially human. Unlike high expression of all six genes in mouse testis, one or two different PRSS genes were predominantly expressed in six primate species. In human testis, PRSS50 was a predominant gene, and the other five PRSS genes were expressed at low levels. Interestingly, promoters of four lowly expressed PRSS genes were marked with both histone H3K4 trimethylation and histone H3K27 trimethylation in human spermatocytes and spermatids, while their orthologous mouse genes were marked only with histone H3K4 trimethylation. Additionally, an ATAC-seq peak in human testis exhibited silencer activity for PRSS45 which is a lowly expressed gene in human but a predominant gene in chimpanzee. These results suggest that bivalent chromatins and an active silencer cooperatively function to achieve appropriate levels of expression for individual PRSS genes during human spermatogenesis. These findings provide mechanistic insights into gene regulation in human spermatogenesis.