Genes Responsible for Maintaining Embryonic Developmental Potential

Discovery of Dux/DUX4 as a major driver of cleavage-stage genes and processes in mammalian embryos.

A major question concerning early embryos involves how early cleavage-stage (two-cell) embryos establish unlimited developmental potential – termed totipotency. Cairns and colleagues identified the multicopy retrogene, DUX4 in humans or Dux in mice, as a transcription factor that is turned on in very early embryos and activates hundreds of genes and retroviral elements during cleavage stage. Remarkably, the expression of Dux efficiently converts mouse embryonic stem cells into 2-cell-embryo-like cells (2CLC) with expanded developmental potential.

Interestingly, these 2CLC can contribute to either embryonic or extra-embryonic (trophectoderm/placenta) cell lineages. Thus, Dux-family proteins appear to play essential roles in determining developmental potential in early embryos. The improper expression of DUX4 underlies the common muscle disease facioscapulohumeral muscular dystrophy (FSHD), and the results from this work provide important and novel information on the typical role of DUX4 that can now be explored in the context of FSHD.

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Conserved roles of mouse DUX and human DUX4 in activating cleavage-stage genes and MERVL/HERVL retrotransposons. Hendrickson PG, Doráis JA, Grow EJ, Whiddon JL, Lim JW, Wike CL, Weaver BD, Pflueger C, Emery BR, Wilcox AL, Nix DA, Peterson CM, Tapscott SJ, Carrell DT, Cairns BR. Nat Genet. 2017 Jun;49(6):925.