Zygotic Genome Activation Revisited: Looking Through the Expression and Function of Zscan4

Curr Top Dev Biol. 2016;120:103-24. doi: 10.1016/bs.ctdb.2016.04.004. Epub 2016 May 31.


Zygotic genome activation (ZGA, a.k.a. zygotic gene activation) is a critical event in development, when the paternally derived genome and maternally derived genome begin to be activated and transcribed after fertilization. Major ZGA occurs at the two-cell stage in mice and the four- to eight-cell stage in human preimplantation embryos. It has been thought that ZGA exists to provide RNAs and proteins supporting embryonic development after supplies stored in oocytes are used up; however, this paradigm does not seem to explain recent findings. For example, many ZGA genes-once activated-are quickly turned off, and thus ZGA forms a transient wave of transcriptional activation. In addition, ZGA genes are not evolutionarily conserved. In this review, we address these issues by focusing on Zscan4 (zinc finger and SCAN domain-containing 4), which was identified for its specific expression in preimplantation embryos during ZGA. Detailed molecular analyses of Zscan4 expression and function have revealed common features of Zscan4-associated events (Z4 events) in mouse embryonic stem cells and ZGA in preimplantation embryos. One feature is a rapid derepression and rerepression of constitutive heterochromatin, which includes pericentromeric major satellites and telomeres, and facultative heterochromatin, which includes retrotransposons and Z4 event-associated genes. We propose that the Z4 event superimposed on ZGA plays a critical role in the maintenance of genome and chromosome integrity in preimplantation embryos by promoting correction of DNA damage and chromosome abnormalities.

Keywords: Chromosome abnormality; DNA damage; Heterochromatin; Preimplantation embryos; Zscan4; Zygotic gene activation; Zygotic genome activation.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA Damage
  • Evolution, Molecular
  • Gene Expression Regulation, Developmental*
  • Genome*
  • Humans
  • Transcription Factors / metabolism*
  • Zygote / metabolism*


  • Transcription Factors