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H3K27me3 timely dictates uterine epithelial transcriptome remodeling and thus transformation essential for normal embryo implantation

Cell Death & Differentiation (2024)Cite this article

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Abstract

Uterine luminal epithelia (LE), the first layer contacting with the blastocyst, acquire receptivity for normal embryo implantation. Besides the well-accepted transcriptional regulation dominated by ovarian estrogen and progesterone for receptivity establishment, the involvement of epigenetic mechanisms remains elusive. This study systematically profiles the transcriptome and genome-wide H3K27me3 distribution in the LE throughout the preimplantation. Combining genetic and pharmacological approaches targeting the PRC2 core enzyme Ezh1/2, we demonstrate that the defective remodeling of H3K27me3 in the preimplantation stage disrupts the differentiation of LE, and derails uterine receptivity, resulting in implantation failure. Specifically, crucial epithelial genes, Pgr, Gata2, and Sgk1, are transcriptionally silenced through de novo deposition of H3K27me3 for LE transformation, and their sustained expression in the absence of H3K27me3 synergistically confines the nuclear translocation of FOXO1. Further functional studies identify several actin-associated genes, including Arpin, Tmod1, and Pdlim2, as novel direct targets of H3K27me3. Their aberrantly elevated expression impedes the morphological remodeling of LE, a hindrance alleviated by treatment with cytochalasin D which depolymerizes F-actin. Collectively, this study uncovers a previously unappreciated epigenetic regulatory mechanism for the transcriptional silencing of key LE genes via H3K27me3, essential for LE differentiation and thus embryo implantation.

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Fig. 1: The dynamic transcriptomic landscape of luminal epithelia in preimplantation uteri.
Fig. 2: H3K27me3 dynamics for transcriptional silencing of luminal epithelial genes.
Fig. 3: Uterine-specific ablation of H3K27me3 resulted in embryo implantation failure.
Fig. 4: The deficiency of H3K27me3 led to aberrant expressions of uterine receptivity-related genes.
Fig. 5: Luminal epithelial differentiation paused from D4 to D4.5 in the absence of H3K27me3.
Fig. 6: A set of luminal epithelial candidate genes was modulated by H3K27me3.
Fig. 7: H3K27me3 mediated timely transcriptional repression of Pgr, Gata2, and Sgk1, ensuring the nuclear entry of FOXO1.
Fig. 8: H3K27me3 repressed F-actin regulators to coordinate morphological remodeling in the LE.

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Data availability

RNA-seq and CUT&Tag raw data generated in this study have been deposited at the National Center for Biotechnology Information Sequence Read Archive under accession number PRJNA1046974 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1046974).

Code availability

Code is availability upon request by contacting the corresponding author.

References

  1. Wang H, Dey SK. Roadmap to embryo implantation: clues from mouse models. Nat Rev Genet. 2006;7:185–99.

    Article  PubMed  Google Scholar 

  2. Cha J, Sun X, Dey SK. Mechanisms of implantation: strategies for successful pregnancy. Nat Med. 2012;18:1754–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lejeune B, Van Hoeck J, Leroy F. Transmitter role of the luminal uterine epithelium in the induction of decidualization in rats. J Reprod Fertil. 1981;61:235–40.

    Article  CAS  PubMed  Google Scholar 

  4. Denker HW. Implantation - a Cell Biological Paradox. J Exp Zool. 1993;266:541–58.

    Article  CAS  PubMed  Google Scholar 

  5. Xiao S, Diao H, Zhao F, Li R, He N, Ye X. Differential gene expression profiling of mouse uterine luminal epithelium during periimplantation. Reprod Sci. 2014;21:351–62.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Ye X. Uterine Luminal Epithelium as the Transient Gateway for Embryo Implantation. Trends Endocrinol Metab. 2020;31:165–80.

    Article  CAS  PubMed  Google Scholar 

  7. Fukui Y, Hirota Y, Matsuo M, Gebril M, Akaeda S, Hiraoka T, et al. Uterine receptivity, embryo attachment, and embryo invasion: Multistep processes in embryo implantation. Reprod Med Biol. 2019;18:234–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Pawar S, Starosvetsky E, Orvis GD, Behringer RR, Bagchi IC, Bagchi MK. STAT3 regulates uterine epithelial remodeling and epithelial-stromal crosstalk during implantation. Mol Endocrinol. 2013;27:1996–2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Tu Z, Wang Q, Cui T, Wang J, Ran H, Bao H, et al. Uterine RAC1 via Pak1-ERM signaling directs normal luminal epithelial integrity conducive to on-time embryo implantation in mice. Cell Death Differ. 2016;23:169–81.

    Article  CAS  PubMed  Google Scholar 

  10. Ye XQ, Hama K, Contos JJA, Anliker B, Inoue A, Skinner MK, et al. LPA-mediated lysophosphatidic acid signalling in embryo implantation and spacing. Nature. 2005;435:104–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. van Mierlo G, Veenstra GJC, Vermeulen M, Marks H. The Complexity of PRC2 Subcomplexes. Trends Cell Biol. 2019;29:660–71.

    Article  PubMed  Google Scholar 

  12. Margueron R, Reinberg D. The Polycomb complex PRC2 and its mark in life. Nature. 2011;469:343–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, Lee TI, et al. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature. 2006;441:349–53.

    Article  CAS  PubMed  Google Scholar 

  14. Pasini D, Bracken AP, Hansen JB, Capillo M, Helin K. The polycomb group protein Suz12 is required for embryonic stem cell differentiation. Mol Cell Biol. 2007;27:3769–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Duan R, Du W, Guo W. EZH2: a novel target for cancer treatment. J Hematol Oncol. 2020;13:104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chammas P, Mocavini I, Di Croce L. Engaging chromatin: PRC2 structure meets function. Br J Cancer. 2020;122:315–28.

    Article  CAS  PubMed  Google Scholar 

  17. Osokine I, Siewiera J, Rideaux D, Ma S, Tsukui T, Erlebacher A. Gene silencing by EZH2 suppresses TGF-beta activity within the decidua to avert pregnancy-adverse wound healing at the maternal-fetal interface. Cell Rep. 2022;38:110329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Fukui Y, Hirota Y, Aikawa S, Sakashita A, Shimizu-Hirota R, Takeda N, et al. The EZH2-PRC2-H3K27me3 axis governs the endometrial cell cycle and differentiation for blastocyst invasion. Cell Death Dis. 2023;14:320.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sirohi VK, Medrano TI, Kannan A, Bagchi IC, Cooke PS. Uterine-specific Ezh2 deletion enhances stromal cell senescence and impairs placentation, resulting in pregnancy loss. iScience. 2023;26:107028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Nancy P, Tagliani E, Tay CS, Asp P, Levy DE, Erlebacher A. Chemokine gene silencing in decidual stromal cells limits T cell access to the maternal-fetal interface. Science. 2012;336:1317–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Nancy P, Siewiera J, Rizzuto G, Tagliani E, Osokine I, Manandhar P, et al. H3K27me3 dynamics dictate evolving uterine states in pregnancy and parturition. J Clin Invest. 2018;128:233–47.

    Article  PubMed  Google Scholar 

  22. Zhang Q, Paria BC. Importance of uterine cell death, renewal, and their hormonal regulation in hamsters that show progesterone-dependent implantation. Endocrinology. 2006;147:2215–27.

    Article  CAS  PubMed  Google Scholar 

  23. Sharkey DJ, Glynn DJ, Schjenken JE, Tremellen KP, Robertson SA. Interferon-gamma inhibits seminal plasma induction of colony-stimulating factor 2 in mouse and human reproductive tract epithelial cells. Biol Reprod. 2018;99:514–26.

    Article  PubMed  Google Scholar 

  24. Jeong JW, Lee KY, Kwak I, White LD, Hilsenbeck SG, Lydon JP, et al. Identification of murine uterine genes regulated in a ligand-dependent manner by the progesterone receptor. Endocrinology. 2005;146:3490–505.

    Article  CAS  PubMed  Google Scholar 

  25. Liu X, Bie XM, Lin X, Li M, Wang H, Zhang X, et al. Uncovering the transcriptional regulatory network involved in boosting wheat regeneration and transformation. Nat Plants. 2023;9:908–25.

    Article  CAS  PubMed  Google Scholar 

  26. Konze KD, Ma A, Li F, Barsyte-Lovejoy D, Parton T, Macnevin CJ, et al. An orally bioavailable chemical probe of the Lysine Methyltransferases EZH2 and EZH1. ACS Chem Biol. 2013;8:1324–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zhang S, Lin H, Kong S, Wang S, Wang H, Wang H, et al. Physiological and molecular determinants of embryo implantation. Mol Asp Med. 2013;34:939–80.

    Article  Google Scholar 

  28. Xin QL, Qiu JT, Cui S, Xia GL, Wang HB. Transcriptional activation of nuclear estrogen receptor and progesterone receptor and its regulation. Sheng Li Xue Bao. 2016;68:435–54.

    PubMed  Google Scholar 

  29. Xin Q, Kong S, Yan J, Qiu J, He B, Zhou C, et al. Polycomb subunit BMI1 determines uterine progesterone responsiveness essential for normal embryo implantation. J Clin Invest. 2018;128:175–89.

    Article  PubMed  Google Scholar 

  30. Kurihara I, Lee DK, Petit FG, Jeong J, Lee K, Lydon JP, et al. COUP-TFII mediates progesterone regulation of uterine implantation by controlling ER activity. PLoS Genet. 2007;3:1053–64.

    CAS  Google Scholar 

  31. Li QX, Kannan A, DeMayo FJ, Lydon JP, Cooke PS, Yamagishi H, et al. The Antiproliferative Action of Progesterone in Uterine Epithelium Is Mediated by Hand2. Science. 2011;331:912–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Rodriguez CI, Cheng JG, Liu L, Stewart CL. Cochlin, a secreted von Willebrand factor type a domain-containing factor, is regulated by leukemia inhibitory factor in the uterus at the time of embryo implantation. Endocrinology. 2004;145:1410–8.

    Article  CAS  PubMed  Google Scholar 

  33. Hayashi K, Erikson DW, Tilford SA, Bany BM, Maclean JA, Rucker EB, et al. Genes in the Mouse Uterus: Potential Regulation of Implantation. Biol Reprod. 2009;80:989–1000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Carson DD, Julian J, Lessey BA, Prakobphol A, Fisher SJ. MUC1 is a scaffold for selectin ligands in the human uterus. Front Biosci. 2006;11:2903–8.

    Article  CAS  PubMed  Google Scholar 

  35. Carson DD, DeSouza MM, Regisford EG. Mucin and proteoglycan functions in embryo implantation. Bioessays. 1998;20:577–83.

    Article  CAS  PubMed  Google Scholar 

  36. Daikoku T, Cha J, Sun X, Tranguch S, Xie H, Fujita T, et al. Conditional deletion of Msx homeobox genes in the uterus inhibits blastocyst implantation by altering uterine receptivity. Dev Cell. 2011;21:1014–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Chen JR, Cheng JG, Shatzer T, Sewell L, Hernandez L, Stewart CL. Leukemia inhibitory factor can substitute for nidatory estrogen and is essential to inducing a receptive uterus for implantation but is not essential for subsequent embryogenesis. Endocrinology. 2000;141:4365–72.

    Article  CAS  PubMed  Google Scholar 

  38. Rosario GX, Hondo E, Jeong JW, Mutalif R, Ye X, Yee LX, et al. The LIF-mediated molecular signature regulating murine embryo implantation. Biol Reprod. 2014;91:66.

    Article  PubMed  Google Scholar 

  39. Li Y, Martin TE, Hancock JM, Li R, Viswanathan S, Lydon JP, et al. Visualization of preimplantation uterine fluid absorption in mice using Alexa Fluor 488 Hydrazide†. Biol Reprod 2023;108:204–17.

    Article  PubMed  Google Scholar 

  40. Richard C, Gao J, Brown N, Reese J. Aquaporin water channel genes are differentially expressed and regulated by ovarian steroids during the periimplantation period in the mouse. Endocrinology. 2003;144:1533–41.

    Article  CAS  PubMed  Google Scholar 

  41. Deng WB, Tian Z, Liang XH, Wang BC, Yang F, Yang ZM. Progesterone regulation of Na/K-ATPase beta1 subunit expression in the mouse uterus during the peri-implantation period. Theriogenology. 2013;79:1196–203.

    Article  CAS  PubMed  Google Scholar 

  42. Rubel CA, Wu SP, Lin L, Wang T, Lanz RB, Li X, et al. A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function. Cell Rep. 2016;17:1414–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Wu SP, Li R, DeMayo FJ. Progesterone Receptor Regulation of Uterine Adaptation for Pregnancy. Trends Endocrinol Metab. 2018;29:481–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Li R, Wang X, Huang Z, Balaji J, Kim TH, Wang T, et al. The role of epithelial progesterone receptor isoforms in embryo implantation. iScience. 2021;24:103487.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Salker MS, Christian M, Steel JH, Nautiyal J, Lavery S, Trew G, et al. Deregulation of the serum- and glucocorticoid-inducible kinase SGK1 in the endometrium causes reproductive failure. Nat Med. 2011;17:1509–13.

    Article  CAS  PubMed  Google Scholar 

  46. Wetendorf M, Wu SP, Wang X, Creighton CJ, Wang T, Lanz RB, et al. Decreased epithelial progesterone receptor A at the window of receptivity is required for preparation of the endometrium for embryo attachment. Biol Reprod. 2017;96:313–26.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Gebril M, Hirota Y, Aikawa S, Fukui Y, Kaku T, Matsuo M, et al. Uterine Epithelial Progesterone Receptor Governs Uterine Receptivity Through Epithelial Cell Differentiation. Endocrinology. 2020;161:bqaa195.

    Article  PubMed  Google Scholar 

  48. Vasquez YM, Wang X, Wetendorf M, Franco HL, Mo Q, Wang T, et al. FOXO1 regulates uterine epithelial integrity and progesterone receptor expression critical for embryo implantation. PLoS Genet. 2018;14:e1007787.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Murphy CR. Uterine receptivity and the plasma membrane transformation. Cell Res. 2004;14:259–67.

    Article  PubMed  Google Scholar 

  50. Murphy CR. The cytoskeleton of uterine epithelial cells: a new player in uterine receptivity and the plasma membrane transformation. Hum Reprod Update. 1995;1:567–80.

    Article  CAS  PubMed  Google Scholar 

  51. Kalam SN, Dowland S, Lindsay L, Murphy CR. Microtubules are reorganised and fragmented for uterine receptivity. Cell Tissue Res. 2018;374:667–77.

    Article  CAS  PubMed  Google Scholar 

  52. Moore CL, Cheng D, Shami GJ, Murphy CR. Correlated light and electron microscopy observations of the uterine epithelial cell actin cytoskeleton using fluorescently labeled resin-embedded sections. Micron. 2016;84:61–6.

    Article  CAS  PubMed  Google Scholar 

  53. Shoji K, Ohashi K, Sampei K, Oikawa M, Mizuno K. Cytochalasin D acts as an inhibitor of the actin-cofilin interaction. Biochem Biophys Res Commun. 2012;424:52–7.

    Article  CAS  PubMed  Google Scholar 

  54. Liu MY, Deng WB, Tang L, Liu M, Bao HL, Guo CH, et al. Menin directs regionalized decidual transformation through epigenetically setting PTX3 to balance FGF and BMP signaling. Nat Commun. 2022;13:1006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ma WG, Song H, Das SK, Paria BC, Dey SK. Estrogen is a critical determinant that specifies the duration of the window of uterine receptivity for implantation. Proc Natl Acad Sci USA. 2003;100:2963–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Chen Y, Ni H, Ma XH, Hu SJ, Luan LM, Ren G, et al. Global analysis of differential luminal epithelial gene expression at mouse implantation sites. J Mol Endocrinol. 2006;37:147–61.

    Article  CAS  PubMed  Google Scholar 

  57. Wang P, Du S, Guo C, Ni Z, Huang Z, Deng N, et al. The presence of blastocyst within the uteri facilitates lumenal epithelium transformation for implantation via upregulating lysosome proteostasis activity. Autophagy. 2024;20:58–75.

  58. Grimaldi G, Christian M, Steel JH, Henriet P, Poutanen M, Brosens JJ. Down-regulation of the histone methyltransferase EZH2 contributes to the epigenetic programming of decidualizing human endometrial stromal cells. Mol Endocrinol. 2011;25:1892–903.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Shen X, Liu Y, Hsu YJ, Fujiwara Y, Kim J, Mao X, et al. EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency. Mol Cell. 2008;32:491–502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Xiao S, Li R, El Zowalaty AE, Diao H, Zhao F, Choi Y, et al. Acidification of uterine epithelium during embryo implantation in mice. Biol Reprod. 2017;96:232–43.

    Article  PubMed  Google Scholar 

  61. Cha J, Bartos A, Park C, Sun X, Li Y, Cha SW, et al. Appropriate crypt formation in the uterus for embryo homing and implantation requires Wnt5a-ROR signaling. Cell Rep. 2014;8:382–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Yuan J, Cha J, Deng W, Bartos A, Sun X, Ho HH, et al. Planar cell polarity signaling in the uterus directs appropriate positioning of the crypt for embryo implantation. Proc Natl Acad Sci USA. 2016;113:E8079–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Su IH, Basavaraj A, Krutchinsky AN, Hobert O, Ullrich A, Chait BT, et al. Ezh2 controls B cell development through histone H3 methylation and rearrangement. Nat Immunol. 2003;4:124–31.

    Article  CAS  PubMed  Google Scholar 

  64. Soyal SM, Mukherjee A, Lee KYS, Li J, Li HG, DeMayo FJ, et al. Cre-mediated recombination in cell lineages that express the progesterone receptor. Genesis. 2005;41:58–66.

    Article  CAS  PubMed  Google Scholar 

  65. Sountoulidis A, Liontos A, Nguyen HP, Firsova AB, Fysikopoulos A, Qian XY, et al. SCRINSHOT enables spatial mapping of cell states in tissue sections with single-cell resolution. PLoS Biol. 2020;18:e3000675.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We are grateful to Prof. Francesco DeMayo (National Institute of Environmental Health Sciences), Prof. Thomas Jenuwein (Max Planck Institute for Immunology and Epigenetics), and Prof. Alexander Tartakovsky (The Rockefeller University) for providing us with the Pgr-Cre, Ezh1 knockout, and Ezh2-loxp mice. We also thank the lab members for their helpful discussions.

Funding

The work was supported by the National Key Research and Development Program of China (2022YFC2702500 and 2021YFC2700302); National Natural Science Foundation of China (82288102, 82030040, 82222026, 82122026, and 32270907).

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  1. These authors contributed equally: Na Deng, Gaizhen Li.

Authors and Affiliations

  1. Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361102, Fujian, China

    Na Deng, Gaizhen Li, Leilei Zhang, Peiran Wang, Mengying Liu, Bo He, Yedong Tang, Han Cai, Jinhua Lu, Haibin Wang, Wenbo Deng, Haili Bao & Shuangbo Kong

  2. State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Medicine, Xiamen University, Xiamen, 361102, Fujian, China

    Haibin Wang

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Contributions

ND, SK, HB, HW, designed research; ND, GL, PW, BH, ML, YT, HC, performed research; LZ, WD, analyzed the data; JL, SK, HW, supervised the study. ND, HB, GL, prepared figures and wrote the manuscript.

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Correspondence to Haibin Wang, Wenbo Deng, Haili Bao or Shuangbo Kong.

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Deng, N., Li, G., Zhang, L. et al. H3K27me3 timely dictates uterine epithelial transcriptome remodeling and thus transformation essential for normal embryo implantation. Cell Death Differ (2024). https://doi.org/10.1038/s41418-024-01302-9

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