The earliest embryonic cells have the potential to produce all differentiated tissues, but this totipotency is lost after zygotic genome activation (ZGA), via unknown mechanisms. A recent study in Nature Genetics by Vega-Sendino et al. has identified how the homeobox transcription factor DUXBL regulates development after ZGA and out of stages marked by totipotency in mice.

Next, the authors tested whether DUXBL has a function similar to that of DUX in activating the 2C-stage transcriptional programme that entails ZGA. They generated embryonic stem cells with inducible expression of DUXBL and found that overexpression of DUXBL resulted in fewer embryonic stem cells becoming 2C-like cells and decreased levels of DUX-induced transcription. These findings suggest that DUXBL antagonizes the function of DUX to drive transcription during the 2C stage that is associated with totipotency.