H3K9 tri-methylation at Nanog times differentiation commitment and enables the acquisition of primitive endoderm fate
| العنوان: | H3K9 tri-methylation at Nanog times differentiation commitment and enables the acquisition of primitive endoderm fate |
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| المؤلفون: | Agnès Dubois, Loris Vincenti, Almira Chervova, Maxim V. C. Greenberg, Sandrine Vandormael-Pournin, Déborah Bourc'his, Michel Cohen-Tannoudji, Pablo Navarro |
| المساهمون: | Epigénomique, Prolifération et Identité Cellulaire - Epigenomics, Proliferation and the Identity of Cells (EPIC), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), 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), Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This work was funded by the Labex Revive (Agence Nationale de la Recherche, Investissement d'Avenir, ANR-10-LABX-73), the Institut Pasteur and the Centre National de la Recherche Scientifique. Open access funding provided by the Institut Pasteur. Deposited in PMC for immediate release., We acknowledge the flow cytometry platform of Institut Pasteur as well as L. Bally-Cuif and S. Tajbakhsh for critical reading of the manuscript. P.N. and A.D. acknowledge Ian Chambers for kindly providing TNG cells and Basilia Acurzio and Andrea Riccio for Zfp57 knockout cells., ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), Cohen-Tannoudji, Michel, Laboratoires d'excellence - Stem Cells in Regenerative Biology and Medicine - - REVIVE2010 - ANR-10-LABX-0073 - LABX - VALID |
| المصدر: | Development (Cambridge, England) Development (Cambridge, England), 2022, 149 (17), pp.dev201074. ⟨10.1242/dev.201074⟩ |
| بيانات النشر: | HAL CCSD, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Mouse, Endoderm, Genes, Homeobox, Cell Differentiation, Nanog Homeobox Protein, Nanog, H3K9me3, Histone Code, Mice, ERK, [SDV.BDD] Life Sciences [q-bio]/Development Biology, Animals, Heterogeneity, Molecular Biology, Primitive endoderm, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Embryonic Stem Cells, ZFP57, Developmental Biology |
| الوصف: | Mouse embryonic stem cells have an inherent propensity to explore gene regulatory states associated with either self-renewal or differentiation. This property depends on ERK, which downregulates pluripotency genes such as Nanog. Here, we aimed at identifying repressive histone modifications that would mark Nanog for inactivation in response to ERK activity. We found that the transcription factor ZFP57, which binds methylated DNA to nucleate heterochromatin, is recruited upstream of Nanog, within a region enriched for histone H3 lysine 9 tri-methylation (H3K9me3). Whereas before differentiation H3K9me3 at Nanog depends on ERK, in somatic cells it becomes independent of ERK. Moreover, the loss of H3K9me3 at Nanog, induced by deleting the region or by knocking out DNA methyltransferases or Zfp57, is associated with reduced heterogeneity of NANOG, delayed commitment into differentiation and impaired ability to acquire a primitive endoderm fate. Hence, a network axis centred on DNA methylation, ZFP57 and H3K9me3 links Nanog regulation to ERK activity for the timely establishment of new cell identities. We suggest that establishment of irreversible H3K9me3 at specific master regulators allows the acquisition of particular cell fates during differentiation. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0950-1991 1477-9129 |
| DOI: | 10.1242/dev.201074⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9584fd7f27b37a2a363566bb3518f4f8 https://hal-pasteur.archives-ouvertes.fr/pasteur-03796516 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9584fd7f27b37a2a363566bb3518f4f8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 09501991 14779129 |
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| DOI: | 10.1242/dev.201074⟩ |