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

Peng Yang; Yixuan Wang; Don Hoang; Matthew Tinkham; Anamika Patel; Ming An Sun; Gernot Wolf; Mairead Baker; Huan Chieh Chien; Kuan Yu Nick Lai; Xiaodong Cheng; Che Kun James Shen; Todd S. Macfarlan

doi:10.1126/science.aah6895

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

Peng Yang, Yixuan Wang, Don Hoang, Matthew Tinkham, Anamika Patel, Ming An Sun, Gernot Wolf, Mairead Baker, Huan Chieh Chien, Kuan Yu Nick Lai, Xiaodong Cheng, Che Kun James Shen, Todd S. Macfarlan

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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.

Original language	English (US)
Pages (from-to)	757-759
Number of pages	3
Journal	Science
Volume	356
Issue number	6339
DOIs	https://doi.org/10.1126/science.aah6895
State	Published - May 19 2017
Externally published	Yes

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@article{2d04ef519a084ddda95935d81a5f6304,

title = "Developmental biology: 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 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.",

author = "Peng Yang and Yixuan Wang and Don Hoang and Matthew Tinkham and Anamika Patel and Sun, {Ming An} and Gernot Wolf and Mairead Baker and Chien, {Huan Chieh} and {Nick Lai}, {Kuan Yu} and Xiaodong Cheng and {James Shen}, {Che Kun} and Macfarlan, {Todd S.}",

note = "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.). NGS data have been deposited in the Gene Expression Omnibus (GEO) database (GSE84832).",

year = "2017",

month = may,

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doi = "10.1126/science.aah6895",

language = "English (US)",

volume = "356",

pages = "757--759",

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T2 - A placental growth factor is silenced in mouse embryos by the zinc finger protein ZFP568

AU - Yang, Peng

AU - Wang, Yixuan

AU - Hoang, Don

AU - Tinkham, Matthew

AU - Patel, Anamika

AU - Sun, Ming An

AU - Wolf, Gernot

AU - Baker, Mairead

AU - Chien, Huan Chieh

AU - Nick Lai, Kuan Yu

AU - Cheng, Xiaodong

AU - James Shen, Che Kun

AU - Macfarlan, Todd S.

N1 - 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.). NGS data have been deposited in the Gene Expression Omnibus (GEO) database (GSE84832).

PY - 2017/5/19

Y1 - 2017/5/19

N2 - 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.

AB - 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.

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

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