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

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.

SUBMITTER: Yang P 

PROVIDER: S-EPMC6309218 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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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 <i>Igf2</i> transcript (designated <i>Igf2-P0</i>) in mice. Loss of <i>Zfp568</i>, which causes gastrulation failure, or mutation of the ZFP568-binding site at the <i>Igf2-P  ...[more]

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