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

• Type of Material: Article
• Authors: Peng Yang, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Yixuan Wang, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Don Hoang, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Matthew Tinkham, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Anamika Patel, Emory University; Ming-An Sun, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Gernot Wolf, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Mairead Baker, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Huan-Chieh Chien, National Yang Ming University; Kuan-Yu Nick Lai, National Yang Ming University; Xiaodong Cheng, Emory University; Che-Kun James Shen, National Yang Ming University; Todd S. Macfarlan, Eunice Kennedy Shriver National Institute of Child Health and Human Development
• Language: English
• Date: 2017-05-19
• Publisher: Volgogradskii Gosudarstvennyi Universitet (Volgograd State University)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017, American Association for the Advancement of Science
• Final Published Version (URL): http://dx.doi.org/10.1126/science.aah6895
• Title of Journal or Parent Work: Вестник Волгоградского государственног... / Science Journal of Volgograd State University. History. Area Studies. International Relations
• ISSN: 1998-9938
• Volume: 356
• Issue: 6339
• Start Page: 757
• End Page: 759
• Grant/Funding Information: This work was supported by NIH grants 1ZIAHD008933 (T.S.M.) and GM049245-23 (A.P. and X.C.), Ministry of Science and Technology (MOST) Frontier of Science Award, Academia Sinica Senior Investigator Award (C.-K.J.S.), National Natural Science Foundation of China (NSFC) 31471392, and Future Scientists Exchange Program of the China Scholarship Council (CSC) (Y.W.).
• Keywords: GENE; TISSUES; METHYLATION; Science & Technology - Other Topics; REGION; Multidisciplinary Sciences; CONVERGENT EXTENSION; Science & Technology
• Research Categories: Chemistry, Biochemistry; Biology, Molecular

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 Kruppelassociated 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.