G-quadruplex DNA Structure Resolvase RHAU Regulates Spenrmatogonia Differentiation

The development of germ cells is crucial for the passage and evolution of all species. The precise regulation of gene expression is essential for the development of germ cells. DNA sequences serve as template for gene transcription, and regulatory element for gene expression regulation.Here, we first introduced the roles of a special DNA structure, G-quadruplex (G4) structure, and its unwinding enzyme, RHAU, in spermatogenesis. Our finding indicated the dynamic changes of G4 structure and RHAU displaying a dynamic change during spermatogenesis were important for spermatogenesis. The deficiency of RHAU altered the level of G4 structure and thus led to the deregulation of a number of genes, eventually caused spermatogenesis failure beginning at the spermatogonia differentiation stage. Among these changed genes, an oncogene and stem cell differentiation marker gene, c-kit, with G4 structures at its promoter, was validated as a direct target of RHAU by gel-shift assay. This finding revealed the important role of G4 structure and its unwinding enzyme RHAU in mammalian male germ cell development.