DUX-family Transcription Factors Regulate Zygotic Genome Activation in Placental Mammals

Nat Genet. 2017 Jun;49(6):941-945. doi: 10.1038/ng.3858. Epub 2017 May 1.

Abstract

In animal embryos, transcription is mostly silent for several cell divisions, until the release of the first major wave of embryonic transcripts through so-called zygotic genome activation (ZGA). Maternally provided ZGA-triggering factors have been identified in Drosophila melanogaster and Danio rerio, but their mammalian homologs are still undefined. Here, we provide evidence that the DUX family of transcription factors is essential to this process in mice and potentially in humans. First, human DUX4 and mouse Dux are both expressed before ZGA in their respective species. Second, both orthologous proteins bind the promoters of ZGA-associated genes and activate their transcription. Third, Dux knockout in mouse embryonic stem cells (mESCs) prevents the cells from cycling through a 2-cell-like state. Finally, zygotic depletion of Dux leads to impaired early embryonic development and defective ZGA. We conclude that DUX-family proteins are key inducers of zygotic genome activation in placental mammals.

MeSH terms

  • Animals
  • Binding Sites
  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • Dogs
  • Embryonic Stem Cells / physiology
  • Evolution, Molecular
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Mice, Knockout
  • Mice, Transgenic
  • Myoblasts / cytology
  • Myoblasts / physiology
  • Promoter Regions, Genetic
  • Retroelements
  • Transcription Factors / genetics
  • Zygote*

Substances

  • DUX4L1 protein, human
  • Dux4 protein, mouse
  • Homeodomain Proteins
  • Retroelements
  • Transcription Factors