Contribution of cohesins STAG1 and STAG2 to preimplantation development in mice

Cohesin complexes carrying either STAG1 or STAG2 display functional specificities in both cohesion and genome organization. While any variant is sufficient for cell viability, both are essential for murine embryonic development, and mutations in STAG1 and STAG2 are associated to human syndromes. The requirements and regulation of the cohesin variants in the first stages of development remain unknown. Here, we show that Stag1 and Stag2 gene products are stored in oocytes. Maternal STAG1 persists beyond the 2-cell stage while accumulation of STAG2 depends on zygotic transcription. Despite clear differences in STAG1:STAG2 ratio in the two lineages emerging from the first cell-fate decision, both maternal and zygotic STAG1 and STAG2 are dispensable for viability in preimplantation stages if the other variant is present. However, the absence of STAG2 increases DNA damage in zygotes and affects transcription in blastocysts. These early-stage alterations may contribute to defects leading to embryo lethality by mid-gestation. Imaging and transcriptomic analyses in murine embryos reveal distinct regulation of STAG1 and STAG2; while either cohesin complex is sufficient to complete preimplantation development, the absence of STAG2 affects both DNA repair and transcription.