A placental growth factor is silenced in mouse embryos by the zinc finger protein ZFP568
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 repress...
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Published in | Science (American Association for the Advancement of Science) Vol. 356; no. 6339; pp. 757 - 760 |
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Main Authors | , , , , , , , , , , , , |
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 | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0036-8075 1095-9203 1095-9203 |
DOI: | 10.1126/science.aah6895 |