NDLI: Egr1 protein acts downstream of estrogen-leukemia inhibitory factor (LIF)-STAT3 pathway and plays a role during implantation through targeting Wnt4.

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Egr1 protein acts downstream of estrogen-leukemia inhibitory factor (LIF)-STAT3 pathway and plays a role during implantation through targeting Wnt4.

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Egr1 protein acts downstream of estrogen-leukemia inhibitory factor (LIF)-STAT3 pathway and plays a role during implantation through targeting Wnt4.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Cao, Yu-jing Yang, Zeng-ming Li, Ming Wang, Tong-song Duan, En-kui Feng, Xu-hui Zhao, Zhen-ao Liang, Xiao-huan Deng, Wen-bo
Description	Author Affiliation: Liang XH ( From the College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.); Deng WB ( From the College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.); Li M ( College of Life Science, Xiamen University, Xiamen 361005, China.); Zhao ZA ( State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Science, Beijing 100101, China, and.); Wang TS ( Department of Biology, Shantou University, Shantou 515063, China.); Feng XH ( College of Life Science, Xiamen University, Xiamen 361005, China.); Cao YJ ( State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Science, Beijing 100101, China, and.); Duan EK ( State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Science, Beijing 100101, China, and.); Yang ZM ( From the College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China, zmyang@scau.edu.cn.)
Abstract	Embryo implantation is a highly synchronized process between an activated blastocyst and a receptive uterus. Successful implantation relies on the dynamic interplay of estrogen and progesterone, but the key mediators underlying embryo implantation are not fully understood. Here we show that transcription factor early growth response 1 (Egr1) is regulated by estrogen as a downstream target through leukemia inhibitory factor (LIF) signal transducer and activator of transcription 3 (STAT3) pathway in mouse uterus. Egr1 is localized in the subluminal stromal cells surrounding the implanting embryo on day 5 of pregnancy. Estrogen rapidly, markedly, and transiently enhances Egr1 expression in uterine stromal cells, which fails in estrogen receptor knock-out mouse uteri. STAT3 is phosphorylated by LIF and subsequently recruited on Egr1 promoter to induce its expression. Our results of Egr1 expression under induced decidualization in vivo and in vitro show that Egr1 is rapidly induced after deciduogenic stimulus. Egr1 knockdown can inhibit in vitro decidualization of cultured uterine stromal cells. Chromatin immunoprecipitation data show that Egr1 is recruited to the promoter of wingless-related murine mammary tumor virus integration site 4 (Wnt4). Collectively, our study presents for the first time that estrogen regulates Egr1 expression through LIF-STAT3 signaling pathway in mouse uterus, and Egr1 functions as a critical mediator of stromal cell decidualization by regulating Wnt4.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	34
Volume Number	289
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2014-08-22
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Early Growth Response Protein 1 Metabolism Embryo Implantation Estrogens Leukemia Inhibitory Factor STAT3 Transcription Factor Wnt4 Protein Animals Chromatin Immunoprecipitation DNA Primers Genetics Fluorescent Antibody Technique Gene Knockdown Techniques In Situ Hybridization Mice Real-Time Polymerase Chain Reaction Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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