Abstract

Mammalian pregnancy depends on the ability of the uterus to support embryo implantation. Previous studies reveal the Sox17 gene as a downstream target of the Pgr-Gata2-dependent transcription network that directs genomic actions in the uterine endometrium receptive for embryo implantation. Here, we report that ablating Sox17 in the uterine epithelium impairs leukemia inhibitory factor (LIF) and Indian hedgehog homolog (IHH) signaling, leading to failure of embryo implantation. In vivo deletion of the SOX17-binding region 19 kb upstream of the Ihh locus by CRISPR-Cas technology reduces Ihh expression specifically in the uterus and alters proper endometrial epithelial–stromal interactions, thereby impairing pregnancy. This SOX17-binding interval is also bound by GATA2, FOXA2, and PGR. This cluster of transcription factor binding is common in 737 uterine genes and may represent a key regulatory element essential for uterine epithelial gene expression.

Details

Title
SOX17 regulates uterine epithelial–stromal cross-talk acting via a distal enhancer upstream of Ihh
Author
Wang, Xiaoqiu 1   VIAFID ORCID Logo  ; Li, Xilong 2 ; Wang, Tianyuan 3 ; San-Pin, Wu 4 ; Jeong, Jae-Wook 5 ; Kim, Tae Hoon 5 ; Young, Steven L 6 ; Lessey, Bruce A 7 ; Lanz, Rainer B 8 ; Lydon, John P 8 ; DeMayo, Francesco J 4 

1  Reproductive and Development Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA; Department of Animal Science, North Carolina State University, Raleigh, NC, USA 
2  Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA; Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China 
3  Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA 
4  Reproductive and Development Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA 
5  Department of Obstetrics and Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI, USA 
6  Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC, USA 
7  Deptartment of Obstetrics and Gynecology, University of South Carolina School of Medicine, Greenville, SC, USA 
8  Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA 
Pages
1-14
Publication year
2018
Publication date
Oct 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-06652-w
ProQuest document ID
2124750432
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.