The H2A.Z histone variant integrates Wnt signaling in intestinal epithelial homeostasis
| Autor: | Fabrice Escaffit, Jérémie Rispal, Lucie Baron, Martine Chevillard-Briet, Jean-François Beaulieu, Didier Trouche |
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| Přispěvatelé: | Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Centre National de la Recherche Scientifique (CNRS), Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Faculté de médecine et des sciences de la santé [Sherbrooke] (UdeS), Université de Sherbrooke (UdeS) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Cell General Physics and Astronomy 02 engineering and technology Histones Mice Homeostasis Protein Isoforms CDX2 Transcription Factor Intestinal Mucosa lcsh:Science Wnt Signaling Pathway ComputingMilieux_MISCELLANEOUS Mice Knockout Multidisciplinary biology Intestinal stem cells Wnt signaling pathway Gene silencing Cell Differentiation 021001 nanoscience & nanotechnology Chromatin 3. Good health Cell biology Histone medicine.anatomical_structure embryonic structures Stem cell Signal transduction 0210 nano-technology animal structures Science Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences medicine Animals Humans Cell Proliferation Cell growth Epithelial Cells [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Small intestine General Chemistry HCT116 Cells Mice Inbred C57BL 030104 developmental biology Gene Expression Regulation biology.protein lcsh:Q Caco-2 Cells |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-14 (2019) Nature Communications Nature Communications, Nature Publishing Group, 2019, 10 (1), ⟨10.1038/s41467-019-09899-z⟩ |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-019-09899-z⟩ |
| Popis: | The Tip60/p400 chromatin-modifying complex, which is involved in the incorporation and post-translational modification of the H2A.Z histone variant, regulates cell proliferation and important signaling pathways, such as Wnt. Here, we study the involvement of H2A.Z in intestinal epithelial homeostasis, which is dependent on the finely-tuned equilibrium between stem cells renewal and differentiation, under the control of such pathway. We use cell models and inducible knock-out mice to study the impact of H2A.Z depletion on intestinal homeostasis. We show that H2A.Z is essential for the proliferation of human cancer and normal intestinal crypt cells and negatively controls the expression of a subset of differentiation markers, in cultured cells and mice. H2A.Z impairs the recruitment of the intestine-specific transcription factor CDX2 to chromatin, is itself a target of the Wnt pathway and thus, acts as an integrator for Wnt signaling in the control of intestinal epithelial cell fate and homeostasis. The histone variant, H2A.Z is known to regulate gene expression and cell proliferation. Here the authors show that H2A.Z has a central role in the control of intestinal epithelial homeostasis in mice, by preventing terminal differentiation of intestinal progenitors. |
| Databáze: | OpenAIRE |
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