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

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Science  19 May 2017:
Vol. 356, Issue 6339, pp. 757-759
DOI: 10.1126/science.aah6895

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Embryo viability relies on placental repression

The insulin-like growth factor (IGF) signaling pathway controls maternal supply of and fetal demands for nutrients. Yang et al. report that the essential KRAB–zinc finger protein ZFP568 specifically and directly represses a placental-specific IGF2 transcript during early mouse development. Elimination of ZFP568 in vivo leads to the inappropriate early activation of transcription, which results in embryonic death owing to overexpression of IGF2 peptide. Thus, the specific, targeted preimplantation repression of a promoter is essential for viability.

Science, this issue p. 757

Abstract

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.

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