Molecular Mechanisms of Trophoblast Dysfunction Mediated by Imbalance between STOX1 Isoforms
Summary: STOX1 is a transcription factor involved in preeclampsia and Alzheimer disease. We show that the knock-down of the gene induces rather mild effect on gene expression in trophoblast cell lines (BeWo). We identified binding sites of STOX1 shared by the two major isoforms, STOX1A and STOX1B. P...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-05-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220302716 |
| _version_ | 1830488745692889088 |
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| author | Aurélien Ducat Betty Couderc Anthony Bouter Louise Biquard Rajaa Aouache Bruno Passet Ludivine Doridot Marie-Benoîte Cohen Pascale Ribaux Clara Apicella Irène Gaillard Sophia Palfray Yulian Chen Alexandra Vargas Amélie Julé Léo Frelin Julie Cocquet Camino Ruano San Martin Sébastien Jacques Florence Busato Jorg Tost Céline Méhats Paul Laissue Jean-Luc Vilotte Francisco Miralles Daniel Vaiman |
| author_facet | Aurélien Ducat Betty Couderc Anthony Bouter Louise Biquard Rajaa Aouache Bruno Passet Ludivine Doridot Marie-Benoîte Cohen Pascale Ribaux Clara Apicella Irène Gaillard Sophia Palfray Yulian Chen Alexandra Vargas Amélie Julé Léo Frelin Julie Cocquet Camino Ruano San Martin Sébastien Jacques Florence Busato Jorg Tost Céline Méhats Paul Laissue Jean-Luc Vilotte Francisco Miralles Daniel Vaiman |
| author_sort | Aurélien Ducat |
| collection | DOAJ |
| description | Summary: STOX1 is a transcription factor involved in preeclampsia and Alzheimer disease. We show that the knock-down of the gene induces rather mild effect on gene expression in trophoblast cell lines (BeWo). We identified binding sites of STOX1 shared by the two major isoforms, STOX1A and STOX1B. Profiling gene expression of cells overexpressing either STOX1A or STOX1B, we identified genes downregulated by both isoforms, with a STOX1 binding site in their promoters. Among those, STOX1-induced Annexin A1 downregulation led to abolished membrane repair in BeWo cells. By contrast, overexpression of STOX1A or B has opposite effects on trophoblast fusion (acceleration and inhibition, respectively) accompanied by syncytin genes deregulation. Also, STOX1A overexpression led to abnormal regulation of oxidative and nitrosative stress. In sum, our work shows that STOX1 isoform imbalance is a cause of gene expression deregulation in the trophoblast, possibly leading to placental dysfunction and preeclampsia. |
| first_indexed | 2024-12-21T19:25:44Z |
| format | Article |
| id | doaj.art-b54fcc60ee1d4939917d4e09e86f70c3 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-21T19:25:44Z |
| publishDate | 2020-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-b54fcc60ee1d4939917d4e09e86f70c32022-12-21T18:52:51ZengElsevieriScience2589-00422020-05-01235Molecular Mechanisms of Trophoblast Dysfunction Mediated by Imbalance between STOX1 IsoformsAurélien Ducat0Betty Couderc1Anthony Bouter2Louise Biquard3Rajaa Aouache4Bruno Passet5Ludivine Doridot6Marie-Benoîte Cohen7Pascale Ribaux8Clara Apicella9Irène Gaillard10Sophia Palfray11Yulian Chen12Alexandra Vargas13Amélie Julé14Léo Frelin15Julie Cocquet16Camino Ruano San Martin17Sébastien Jacques18Florence Busato19Jorg Tost20Céline Méhats21Paul Laissue22Jean-Luc Vilotte23Francisco Miralles24Daniel Vaiman25Institut Cochin, U1016, INSERM, UMR 8504 CNRS, Université Paris Descartes, Paris 75014, FranceInstitut Cochin, U1016, INSERM, UMR 8504 CNRS, Université Paris Descartes, Paris 75014, FranceInstitute of Chemistry and Biology of Membranes and Nano-objects, UMR 5248, CNRS, University of Bordeaux, IPB, 33600 Pessac, FranceInstitut Cochin, U1016, INSERM, UMR 8504 CNRS, Université Paris Descartes, Paris 75014, FranceInstitut Cochin, U1016, INSERM, UMR 8504 CNRS, Université Paris Descartes, Paris 75014, FranceUniversité Paris-Saclay, INRAE, AgroParisTech, UMR1313-GABI, 78350, Jouy-en-Josas, FranceInstitut Cochin, U1016, INSERM, UMR 8504 CNRS, Université Paris Descartes, Paris 75014, FranceDepartment of Gynecology Obstetrics, Faculty of Medicine, University of Geneva, 1205 Geneva, SwitzerlandDepartment of Gynecology Obstetrics, Faculty of Medicine, University of Geneva, 1205 Geneva, SwitzerlandInstitut Cochin, U1016, INSERM, UMR 8504 CNRS, Université Paris Descartes, Paris 75014, FranceInstitut Cochin, U1016, INSERM, UMR 8504 CNRS, Université Paris Descartes, Paris 75014, FranceInstitut Cochin, U1016, INSERM, UMR 8504 CNRS, Université Paris Descartes, Paris 75014, FranceInstitut Cochin, U1016, INSERM, UMR 8504 CNRS, Université Paris Descartes, Paris 75014, FranceInstitut Cochin, U1016, INSERM, UMR 8504 CNRS, Université Paris Descartes, Paris 75014, FranceInstitut Cochin, U1016, INSERM, UMR 8504 CNRS, Université Paris Descartes, Paris 75014, FranceInstitute of Chemistry and Biology of Membranes and Nano-objects, UMR 5248, CNRS, University of Bordeaux, IPB, 33600 Pessac, FranceInstitut Cochin, U1016, INSERM, UMR 8504 CNRS, Université Paris Descartes, Paris 75014, FranceInstitut Cochin, U1016, INSERM, UMR 8504 CNRS, Université Paris Descartes, Paris 75014, FranceInstitut Cochin, U1016, INSERM, UMR 8504 CNRS, Université Paris Descartes, Paris 75014, FranceLaboratory for Epigenetics and Environment, Institut de Biologie François Jacob, Commissariat àl’Energie Atomique, Evry 91057, FranceLaboratory for Epigenetics and Environment, Institut de Biologie François Jacob, Commissariat àl’Energie Atomique, Evry 91057, FranceInstitut Cochin, U1016, INSERM, UMR 8504 CNRS, Université Paris Descartes, Paris 75014, FranceBiopas Laboratoires, BIOPAS GROUP, Bogotá, ColombiaUniversité Paris-Saclay, INRAE, AgroParisTech, UMR1313-GABI, 78350, Jouy-en-Josas, FranceInstitut Cochin, U1016, INSERM, UMR 8504 CNRS, Université Paris Descartes, Paris 75014, FranceInstitut Cochin, U1016, INSERM, UMR 8504 CNRS, Université Paris Descartes, Paris 75014, France; Corresponding authorSummary: STOX1 is a transcription factor involved in preeclampsia and Alzheimer disease. We show that the knock-down of the gene induces rather mild effect on gene expression in trophoblast cell lines (BeWo). We identified binding sites of STOX1 shared by the two major isoforms, STOX1A and STOX1B. Profiling gene expression of cells overexpressing either STOX1A or STOX1B, we identified genes downregulated by both isoforms, with a STOX1 binding site in their promoters. Among those, STOX1-induced Annexin A1 downregulation led to abolished membrane repair in BeWo cells. By contrast, overexpression of STOX1A or B has opposite effects on trophoblast fusion (acceleration and inhibition, respectively) accompanied by syncytin genes deregulation. Also, STOX1A overexpression led to abnormal regulation of oxidative and nitrosative stress. In sum, our work shows that STOX1 isoform imbalance is a cause of gene expression deregulation in the trophoblast, possibly leading to placental dysfunction and preeclampsia.http://www.sciencedirect.com/science/article/pii/S2589004220302716Reproductive MedicineMolecular BiologyDevelopmental Biology |
| spellingShingle | Aurélien Ducat Betty Couderc Anthony Bouter Louise Biquard Rajaa Aouache Bruno Passet Ludivine Doridot Marie-Benoîte Cohen Pascale Ribaux Clara Apicella Irène Gaillard Sophia Palfray Yulian Chen Alexandra Vargas Amélie Julé Léo Frelin Julie Cocquet Camino Ruano San Martin Sébastien Jacques Florence Busato Jorg Tost Céline Méhats Paul Laissue Jean-Luc Vilotte Francisco Miralles Daniel Vaiman Molecular Mechanisms of Trophoblast Dysfunction Mediated by Imbalance between STOX1 Isoforms iScience Reproductive Medicine Molecular Biology Developmental Biology |
| title | Molecular Mechanisms of Trophoblast Dysfunction Mediated by Imbalance between STOX1 Isoforms |
| title_full | Molecular Mechanisms of Trophoblast Dysfunction Mediated by Imbalance between STOX1 Isoforms |
| title_fullStr | Molecular Mechanisms of Trophoblast Dysfunction Mediated by Imbalance between STOX1 Isoforms |
| title_full_unstemmed | Molecular Mechanisms of Trophoblast Dysfunction Mediated by Imbalance between STOX1 Isoforms |
| title_short | Molecular Mechanisms of Trophoblast Dysfunction Mediated by Imbalance between STOX1 Isoforms |
| title_sort | molecular mechanisms of trophoblast dysfunction mediated by imbalance between stox1 isoforms |
| topic | Reproductive Medicine Molecular Biology Developmental Biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220302716 |
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