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Temporal and regional X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing

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Titel: Temporal and regional X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing
Autoren: Roidor, Clara, Syx, Laurène, Beyne, Emmanuelle, Raynaud, Peggy, Zielinski, Dina, Teissandier, Aurélie, Lee, Caroline, Walter, Marius, Servant, Nicolas, Chebli, Karim, Bourc’his, Deborah, Surani, M. Azim, Borensztein, Maud
Weitere Verfasser: Borensztein, Maud, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut Curie Paris -Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en Biologie cellulaire de Montpellier (CRBM), Génétique et Biologie du Développement, Institut Curie Paris -Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge UK (CAM), Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)
Quelle: Nature Structural & Molecular Biology. 32:926-939
Verlagsinformationen: Springer Science and Business Media LLC, 2025.
Publikationsjahr: 2025
Schlagwörter: Molecular Biology/Genomics [q-bio.GN], [SDV.BDD.GAM] Life Sciences [q-bio]/Development Biology/Gametogenesis, X-chromosome inactivation, Primordial Germ Cells, [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Reprogramming, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Germ Cell, Molecular Biology/Molecular biology, WGBS, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Chromatin &, scRNA-seq, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Dosage compensation, transcription, [SDV.BDD]Life Sciences [q-bio]/Development Biology, 20 CUT&RUN, amp, [SDV.BDD.GAM]Life Sciences [q-bio]/Development Biology/Gametogenesis
Beschreibung: Random X-chromosome inactivation is a hallmark of female mammalian somatic cells. This epigenetic mechanism, mediated by the long noncoding RNA Xist, occurs in the early embryo and is stably maintained throughout life, although inactivation is lost during primordial germ cell (PGC) development. Using a combination of single-cell allele-specific RNA sequencing and low-input chromatin profiling on developing mouse PGCs, we provide a detailed map of X-linked gene reactivation. Despite the absence of Xist expression, PGCs still harbor a fully silent X chromosome at embryonic day 9.5 (E9.5). Subsequently, X-linked genes undergo gradual and distinct regional reactivation. At E12.5, a substantial part of the inactive X chromosome resists reactivation, retaining an epigenetic memory of its silencing. Our findings define the orchestration of reactivation of the inactive X chromosome, a key event in female PGC reprogramming with direct implications for reproduction.
Publikationsart: Article
Dateibeschreibung: application/pdf
Sprache: English
ISSN: 1545-9985
1545-9993
DOI: 10.1038/s41594-024-01469-2
Zugangs-URL: https://pubmed.ncbi.nlm.nih.gov/39838109
https://hal.science/hal-04907746v1
https://hal.science/hal-04907746v1/document
https://doi.org/10.1038/s41594-024-01469-2
Rights: Springer Nature TDM
CC BY
Dokumentencode: edsair.doi.dedup.....2020d6928eebc27b4fa4a159fff9baba
Datenbank: OpenAIRE
Beschreibung
Abstract:Random X-chromosome inactivation is a hallmark of female mammalian somatic cells. This epigenetic mechanism, mediated by the long noncoding RNA Xist, occurs in the early embryo and is stably maintained throughout life, although inactivation is lost during primordial germ cell (PGC) development. Using a combination of single-cell allele-specific RNA sequencing and low-input chromatin profiling on developing mouse PGCs, we provide a detailed map of X-linked gene reactivation. Despite the absence of Xist expression, PGCs still harbor a fully silent X chromosome at embryonic day 9.5 (E9.5). Subsequently, X-linked genes undergo gradual and distinct regional reactivation. At E12.5, a substantial part of the inactive X chromosome resists reactivation, retaining an epigenetic memory of its silencing. Our findings define the orchestration of reactivation of the inactive X chromosome, a key event in female PGC reprogramming with direct implications for reproduction.
ISSN:15459985
15459993
DOI:10.1038/s41594-024-01469-2