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

M. S.H. Ko

Research output: Chapter in Book/Report/Conference proceedingChapter

43 Citations (Scopus)


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.

Original languageEnglish
Title of host publicationMammalian Preimplantation Development, 2016
EditorsMelvin L. De Pamphilis
PublisherAcademic Press Inc.
Number of pages22
ISBN (Print)9780128014288
Publication statusPublished - 2016

Publication series

NameCurrent Topics in Developmental Biology
ISSN (Print)0070-2153


  • Chromosome abnormality
  • DNA damage
  • Heterochromatin
  • Preimplantation embryos
  • Zscan4
  • Zygotic gene activation
  • Zygotic genome activation

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology


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