Molecular Determinants of Totipotency

Division Of Basic Sciences - Nci

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Abstract

The transition from maternal to zygotic transcription (ZGA) is a critical process that determines successful development (Figure 1). Only the zygote and the blastomeres from the 2C stage are considered totipotent, because of their ability to develop both embryonic and extra-embryonic tissues. This unlimited potential becomes progressively more restricted as the embryo develops and ZGA is the trigger to promote the exit from totipotency. As a result of the ZGA, the 2C blastomeres induce a unique transcriptional program associated with totipotency including the expression of cleavage stage-specific genes (e. g. Dux or members of Zscan4 cluster) and murine endogenous retrovirus-L (MERVL) retrotransposon elements. Despite the requirement to induce the 2C-associated transcriptional program, efficient and quick silencing when transitioning to the 4C stage is needed for proper development. In this project, we identified the essential role of the homeobox transcription factor DUXBL during the exit from totipotency and the repression of the totipotency-associated transcriptional program. Our findings uncovered an important mechanistic insight during the developmental stage of zygotic genome activation (ZGA) which might have broader implications in how other developmental transcriptional programs are regulated.