Highly conserved epigenetic regulation of BOULE and DAZL is associated with human fertility

Separation of germ cells fromsomatic cells is a widespread feature of animal sexual reproduction, with a core set of germ cell factors conserved among diverse animals. It is not known what controls their conserved gonadspecific expression. Core components of epigenetic machinery are ancient, but its role in conserved tissue expression regulation remains unexplored. We found that promoters of the reproductive genes BOULE and DAZL exhibit differentialDNAmethylation, consistent with their gonad-specific expression inhumansandmice.Lowor little promoter methylationfromthe testicular tissue is attributedto spermatogenic cells of various stages inthe testis.Suchdifferential DNA methylation is present in the orthologous promoters not only of other mammalian species, but also of chickens and fish, supporting a highly conserved epigeneticmechanism. Furthermore, hypermethylation of DAZL andBOULE promoters in human sperm is associated with human infertility. Our data strongly suggest that epigenetic regulation may underlie conserved germ-cell-specific expression, and such a mechanism may play an important role in human fertility.-Zhang, C.,Xue,P., Gao, L.,Chen, X.,Lin,K.,Yang,X., Dai, Y.,Xu, E. Y. Highly conservedepigenetic regulation of BOULE and DAZL is associated with human fertility.