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

Author

Listed:
  • Xiaoqiu Wang

    (National Institute of Environmental Health Sciences
    North Carolina State University)

  • Xilong Li

    (Baylor College of Medicine
    Feed Research Institute, Chinese Academy of Agricultural Sciences)

  • Tianyuan Wang

    (National Institute of Environmental Health Sciences)

  • San-Pin Wu

    (National Institute of Environmental Health Sciences)

  • Jae-Wook Jeong

    (Michigan State University)

  • Tae Hoon Kim

    (Michigan State University)

  • Steven L. Young

    (University of North Carolina)

  • Bruce A. Lessey

    (University of South Carolina School of Medicine)

  • Rainer B. Lanz

    (Baylor College of Medicine)

  • John P. Lydon

    (Baylor College of Medicine)

  • Francesco J. DeMayo

    (National Institute of Environmental Health Sciences)

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.

Suggested Citation

  • Xiaoqiu Wang & Xilong Li & Tianyuan Wang & San-Pin Wu & Jae-Wook Jeong & Tae Hoon Kim & Steven L. Young & Bruce A. Lessey & Rainer B. Lanz & John P. Lydon & Francesco J. DeMayo, 2018. "SOX17 regulates uterine epithelial–stromal cross-talk acting via a distal enhancer upstream of Ihh," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06652-w
    DOI: 10.1038/s41467-018-06652-w
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    Cited by:

    1. Meng Liu & Mengjun Ji & Jianghong Cheng & Yingzhe Li & Yingpu Tian & Hui Zhao & Yang Wang & Sijing Zhu & Leilei Zhang & Xinmei Xu & Gen-Sheng Feng & Xiaohuan Liang & Haili Bao & Yedong Tang & Shuangbo, 2023. "Deciphering a critical role of uterine epithelial SHP2 in parturition initiation at single cell resolution," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Seung Chel Yang & Mira Park & Kwon-Ho Hong & Hyeonwoo La & Chanhyeok Park & Peike Wang & Gaizhen Li & Qionghua Chen & Youngsok Choi & Francesco J. DeMayo & John P. Lydon & David G. Skalnik & Hyunjung , 2023. "CFP1 governs uterine epigenetic landscapes to intervene in progesterone responses for uterine physiology and suppression of endometriosis," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Rong Li & Tianyuan Wang & Ryan M. Marquardt & John P. Lydon & San-Pin Wu & Francesco J. DeMayo, 2023. "TRIM28 modulates nuclear receptor signaling to regulate uterine function," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    4. Sangappa B. Chadchan & Pooja Popli & Zian Liao & Eryk Andreas & Michelle Dias & Tianyuan Wang & Stephanie J. Gunderson & Patricia T. Jimenez & Denise G. Lanza & Rainer B. Lanz & Charles E. Foulds & Di, 2024. "A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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