A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis
Abstract Cellular responses to the steroid hormones, estrogen (E2), and progesterone (P4) are governed by their cognate receptor’s transcriptional output. However, the feed-forward mechanisms that shape cell-type-specific transcriptional fulcrums for steroid receptors are unidentified. Herein, we fo...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46180-4 |
| _version_ | 1797274073644924928 |
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| author | 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 Diana Monsivais Francesco J. DeMayo Hari Krishna Yalamanchili Emily S. Jungheim Jason D. Heaney John P. Lydon Kelle H. Moley Bert W. O’Malley Ramakrishna Kommagani |
| author_facet | 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 Diana Monsivais Francesco J. DeMayo Hari Krishna Yalamanchili Emily S. Jungheim Jason D. Heaney John P. Lydon Kelle H. Moley Bert W. O’Malley Ramakrishna Kommagani |
| author_sort | Sangappa B. Chadchan |
| collection | DOAJ |
| description | Abstract Cellular responses to the steroid hormones, estrogen (E2), and progesterone (P4) are governed by their cognate receptor’s transcriptional output. However, the feed-forward mechanisms that shape cell-type-specific transcriptional fulcrums for steroid receptors are unidentified. Herein, we found that a common feed-forward mechanism between GREB1 and steroid receptors regulates the differential effect of GREB1 on steroid hormones in a physiological or pathological context. In physiological (receptive) endometrium, GREB1 controls P4-responses in uterine stroma, affecting endometrial receptivity and decidualization, while not affecting E2-mediated epithelial proliferation. Of mechanism, progesterone-induced GREB1 physically interacts with the progesterone receptor, acting as a cofactor in a positive feedback mechanism to regulate P4-responsive genes. Conversely, in endometrial pathology (endometriosis), E2-induced GREB1 modulates E2-dependent gene expression to promote the growth of endometriotic lesions in mice. This differential action of GREB1 exerted by a common feed-forward mechanism with steroid receptors advances our understanding of mechanisms that underlie cell- and tissue-specific steroid hormone actions. |
| first_indexed | 2024-03-07T14:53:10Z |
| format | Article |
| id | doaj.art-116dab8ea7be413e937452d604e585f3 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:53:10Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-116dab8ea7be413e937452d604e585f32024-03-05T19:34:40ZengNature PortfolioNature Communications2041-17232024-03-0115111710.1038/s41467-024-46180-4A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosisSangappa B. Chadchan0Pooja Popli1Zian Liao2Eryk Andreas3Michelle Dias4Tianyuan Wang5Stephanie J. Gunderson6Patricia T. Jimenez7Denise G. Lanza8Rainer B. Lanz9Charles E. Foulds10Diana Monsivais11Francesco J. DeMayo12Hari Krishna Yalamanchili13Emily S. Jungheim14Jason D. Heaney15John P. Lydon16Kelle H. Moley17Bert W. O’Malley18Ramakrishna Kommagani19Department of Pathology and Immunology, Baylor College of Medicine, One Baylor PlazaDepartment of Pathology and Immunology, Baylor College of Medicine, One Baylor PlazaDepartment of Pathology and Immunology, Baylor College of Medicine, One Baylor PlazaDepartment of Obstetrics and Gynecology, Center for Reproductive Health Sciences, Washington University School of MedicineDepartment of Pediatrics, Baylor College of Medicine, One Baylor PlazaIntegrative Bioinformatics, National Institute of Environmental Health SciencesDepartment of Obstetrics and Gynecology, Center for Reproductive Health Sciences, Washington University School of MedicineDepartment of Obstetrics and Gynecology, Center for Reproductive Health Sciences, Washington University School of MedicineDepartment of Molecular and Human Genetics, Baylor College of Medicine, One Baylor PlazaDepartment of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor PlazaLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor PlazaDepartment of Pathology and Immunology, Baylor College of Medicine, One Baylor PlazaReproductive and Developmental Biology Laboratory, National Institute of Environmental Health SciencesDepartment of Pediatrics, Baylor College of Medicine, One Baylor PlazaDepartment of Obstetrics and Gynecology, Center for Reproductive Health Sciences, Washington University School of MedicineDepartment of Molecular and Human Genetics, Baylor College of Medicine, One Baylor PlazaDepartment of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor PlazaDepartment of Obstetrics and Gynecology, Center for Reproductive Health Sciences, Washington University School of MedicineDepartment of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor PlazaDepartment of Pathology and Immunology, Baylor College of Medicine, One Baylor PlazaAbstract Cellular responses to the steroid hormones, estrogen (E2), and progesterone (P4) are governed by their cognate receptor’s transcriptional output. However, the feed-forward mechanisms that shape cell-type-specific transcriptional fulcrums for steroid receptors are unidentified. Herein, we found that a common feed-forward mechanism between GREB1 and steroid receptors regulates the differential effect of GREB1 on steroid hormones in a physiological or pathological context. In physiological (receptive) endometrium, GREB1 controls P4-responses in uterine stroma, affecting endometrial receptivity and decidualization, while not affecting E2-mediated epithelial proliferation. Of mechanism, progesterone-induced GREB1 physically interacts with the progesterone receptor, acting as a cofactor in a positive feedback mechanism to regulate P4-responsive genes. Conversely, in endometrial pathology (endometriosis), E2-induced GREB1 modulates E2-dependent gene expression to promote the growth of endometriotic lesions in mice. This differential action of GREB1 exerted by a common feed-forward mechanism with steroid receptors advances our understanding of mechanisms that underlie cell- and tissue-specific steroid hormone actions.https://doi.org/10.1038/s41467-024-46180-4 |
| spellingShingle | 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 Diana Monsivais Francesco J. DeMayo Hari Krishna Yalamanchili Emily S. Jungheim Jason D. Heaney John P. Lydon Kelle H. Moley Bert W. O’Malley Ramakrishna Kommagani A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis Nature Communications |
| title | A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis |
| title_full | A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis |
| title_fullStr | A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis |
| title_full_unstemmed | A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis |
| title_short | A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis |
| title_sort | greb1 steroid receptor feedforward mechanism governs differential greb1 action in endometrial function and endometriosis |
| url | https://doi.org/10.1038/s41467-024-46180-4 |
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