A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis
© 2024. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Nature communications - 15(2024), 1 vom: 02. März, Seite 1947 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chadchan, Sangappa B [VerfasserIn] |
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| Links: |
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| Themen: |
4G7DS2Q64Y |
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| Anmerkungen: |
Date Completed 05.03.2024 Date Revised 11.03.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-024-46180-4 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369215087 |
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| 100 | 1 | |a Chadchan, Sangappa B |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis |
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| 500 | |a Date Revised 11.03.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a 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 | ||
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| 650 | 7 | |a Neoplasm Proteins |2 NLM | |
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| 700 | 1 | |a Popli, Pooja |e verfasserin |4 aut | |
| 700 | 1 | |a Liao, Zian |e verfasserin |4 aut | |
| 700 | 1 | |a Andreas, Eryk |e verfasserin |4 aut | |
| 700 | 1 | |a Dias, Michelle |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Tianyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Gunderson, Stephanie J |e verfasserin |4 aut | |
| 700 | 1 | |a Jimenez, Patricia T |e verfasserin |4 aut | |
| 700 | 1 | |a Lanza, Denise G |e verfasserin |4 aut | |
| 700 | 1 | |a Lanz, Rainer B |e verfasserin |4 aut | |
| 700 | 1 | |a Foulds, Charles E |e verfasserin |4 aut | |
| 700 | 1 | |a Monsivais, Diana |e verfasserin |4 aut | |
| 700 | 1 | |a DeMayo, Francesco J |e verfasserin |4 aut | |
| 700 | 1 | |a Yalamanchili, Hari Krishna |e verfasserin |4 aut | |
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| 700 | 1 | |a O'Malley, Bert W |e verfasserin |4 aut | |
| 700 | 1 | |a Kommagani, Ramakrishna |e verfasserin |4 aut | |
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