The Zscan4 array of genes (Zscan4a, Zscan4b, Zscan4c, Zscan4d, Zscan4e, Zscanf) is transcribed to yield mRNAs (Falco et al. 2007) which are translated to yield protein. The Zscan4 genes, especially Zscan4d, are expressed in 2-cell embryos (Falco et al. 2007). Obox homeobox factors (Obox1,2,3,4,5,6,7,8) bind and activate Zscan4 genes (Ji et al. 2023).
OBOX, a PRD-like homeobox domain TF family (OBOX1-8), are key regulators of mouse ZGA. Mice deficient for maternally-transcribed Obox1/2/5/7 and zygotically-expressed Obox3/4 had a 2-4 cell arrest accompanied by impaired ZGA. Both maternal and zygotic OBOX can bind promoters and/or enhancers of MERVL, Zscan4, Dppa2/3/4, and Nr5a2 in mouse early embryos (Ji et al., 2023). Near 50% of ZGA genes including Zscan4, Dppa4, Nr5a2 were downregulated in 2-cell embryos after knocking out maternal and zygotic Obox. Ectopic expression of OBOX activated a subset of ZGA genes including Dppa4, Gata1/4, Trim43a/b/c, and MERVL repeats in mESCs.