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

• Published in: Science (American Association for the Advancement of Science) Vol. 356; no. 6339; pp. 757 - 760
• Main Authors: Yang, Peng, Wang, Yixuan, Hoang, Don, Tinkham, Matthew, Patel, Anamika, Sun, Ming-An, Wolf, Gernot, Baker, Mairead, Chien, Huan-Chieh, Lai, Kuan-Yu Nick, Cheng, Xiaodong, Shen, Che-Kun James, Macfarlan, Todd S.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 19.05.2017; The American Association for the Advancement of Science
• Subjects: Animals; Binding sites; Embryo, Mammalian - metabolism; Embryos; Female; Fetuses; Gastrulation; Gastrulation - genetics; Gene deletion; Gene Expression Regulation; Gestation; Growth factors; Growth hormone; Insulin; Insulin-like growth factor II; Insulin-Like Growth Factor II - deficiency; Insulin-Like Growth Factor II - genetics; Insulin-like growth factors; Kruppel protein; Mice; Mice, Knockout; Mutation; Nuclear Proteins - deficiency; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Nutrients; Placenta; Placenta - metabolism; Pregnancy; Promoter Regions, Genetic - genetics; Proteins; Repressor Proteins - metabolism; Rodents; Selectivity; Signal transduction; Target recognition; Transcription activation; Transcripts (Written Records); Zinc; Zinc finger proteins
• ISSN: 0036-8075; 1095-9203; 1095-9203
• 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.