SUMMARY The mammalian sperm genome is thought to lack substantial information to regulate future expression after fertilization. Here we show that most promoters in mouse sperm are flanked by well-positioned nucleosomes marked by active histone modifications. Analysis of these modifications suggests that many enhancers and super-enhancers functional in embryonic and adult tissues are already specified in sperm. The sperm genome is bound by CTCF and cohesin at sites that are also present in round spermatids and embryonic stem cells (ESCs). These sites mediate interactions that organize the sperm genome into domains and compartments that overlap extensively with those found in mESCs. These results suggest that sperm carry a rich source of regulatory information, encoded in part by its three-dimensional folding specified by CTCF and cohesin. This information may contribute to future expression during embryonic and adult life, suggesting mechanisms by which environmental effects on the paternal germline are transmitted trans-generationally.

Highlights d ATAC-seq accessibility at sperm and oocyte promoters is maintained in the embryo d Sperm enhancers containing transcription factors are conserved in mammals d Accessible sperm enhancers are also open in oocytes and preimplantation embryos d Interactions mediated by FoxA1 and CTCF and cohesin persist from gametes to embryos

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