A placental growth factor is silenced in mouse embryos by the zinc finger protein ZFP568

Science. 2017 May 19;356(6339):757-759. doi: 10.1126/science.aah6895.


Insulin-like growth factor 2 (IGF2) is the major fetal growth hormone in mammals. We identify zinc finger protein 568 (ZFP568), a member of the rapidly evolving Kruppel-associated box-zinc finger protein (KRAB-ZFP) family linked primarily to silencing of endogenous retroelements, as a direct repressor of a placental-specific Igf2 transcript (designated Igf2-P0) in mice. Loss of Zfp568, which causes gastrulation failure, or mutation of the ZFP568-binding site at the Igf2-P0 promoter causes inappropriate Igf2-P0 activation. Deletion of Igf2 can completely rescue Zfp568 gastrulation phenotypes through late gestation. Our data highlight the exquisite selectivity with which members of the KRAB-ZFP family repress their targets and identify an additional layer of transcriptional control of a key growth factor regulating fetal and placental development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Embryo, Mammalian / metabolism*
  • Female
  • Gastrulation / genetics
  • Gene Expression Regulation
  • Insulin-Like Growth Factor II / deficiency*
  • Insulin-Like Growth Factor II / genetics*
  • Mice
  • Mice, Knockout
  • Mutation
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Placenta / metabolism
  • Pregnancy
  • Promoter Regions, Genetic / genetics
  • Repressor Proteins / metabolism


  • IGF2 protein, mouse
  • Nuclear Proteins
  • Repressor Proteins
  • Zfp568 protein, mouse
  • Insulin-Like Growth Factor II