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 embryonic development in mice, and mutations in STAG1 and STAG2 cause human developmental disorders. In the first stages of development, continuous cell divisions are accompanied by de novo establishment of genome architecture and activation of zygotic transcription to replace maternal products. The requirements and regulation of the two cohesin variants at this time 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 transition, both maternal and zygotic STAG1 and STAG2 are dispensable for viability in preimplantation stages if the other variant is present. STAG2 deficiency, however, increases DNA damage and affects transcription. These early-stage alterations may contribute to defects leading to embryo lethality by mid-gestation.