SOX17 regulates uterine epithelial-stromal cross-talk acting via a distal enhancer upstream of Ihh

文献类型： 外文期刊

第一作者： Wang, Xiaoqiu

作者： Wang, Xiaoqiu;Wu, San-Pin;DeMayo, Francesco J.;Li, Xilong;Lanz, Rainer B.;Lydon, John P.;Wang, Tianyuan;Jeong, Jae-Wook;Kim, Tae Hoon;Young, Steven L.;Lessey, Bruce A.;Wang, Xiaoqiu;Li, Xilong

作者机构：

期刊名称：NATURE COMMUNICATIONS （ 影响因子：14.919； 五年影响因子：15.805 ）

ISSN： 2041-1723

年卷期： 2018 年 9 卷

页码：

收录情况： SCI

摘要： 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.

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