TET1 Directs Chondrogenic Differentiation by Regulating SOX9 Dependent Activation of Col2a1 and Acan In Vitro
| العنوان: | TET1 Directs Chondrogenic Differentiation by Regulating SOX9 Dependent Activation of Col2a1 and Acan In Vitro |
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| المؤلفون: | Piera Smeriglio, Fiorella Carla Grandi, Sarah Elizabeth Brook Taylor, Antoine Zalc, Nidhi Bhutani |
| المساهمون: | Department of Orthopaedic Surgery [Stanford], Stanford Medicine, Stanford University-Stanford University, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Thérapie des maladies du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | JBMR Plus JBMR Plus, The american society for bone and mineral research, 2020, 4 (8), ⟨10.1002/jbm4.10383⟩ JBMR Plus, Vol 4, Iss 8, Pp n/a-n/a (2020) |
| بيانات النشر: | HAL CCSD, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Orthopedic surgery, 5‐HYDROXYMETHYLCYTOSINE (5hmC), METHYLATION, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, EMBRYONIC CARTILAGE DEVELOPMENT, Diseases of the musculoskeletal system, EPIGENETICS, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, CHONDROGENESIS, RC925-935, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], SKELETAL DEVELOPMENT, RD701-811 |
| الوصف: | Skeletal development is a tightly orchestrated process in which cartilage and bone differentiation are intricately intertwined. Recent studies have highlighted the contribution of epigenetic modifications and their writers to skeletal development. Methylated cytosine (5mC) can be oxidized to 5‐hydroxymethylcytosine (5hmC) by the Ten‐eleven‐translocation (TET) enzymes leading to demethylation. We have previously demonstrated that 5hmC is stably accumulated on lineage‐specific genes that are activated during in vitro chondrogenesis in the ATDC5 chondroprogenitors. Knockdown (KD) of Tet1 via short‐hairpin RNAs blocked ATDC5 chondrogenic differentiation. Here, we aimed to provide the mechanistic basis for TET1 function during ATDC5 differentiation. Transcriptomic analysis of Tet1 KD cells demonstrated that 54% of downregulated genes were SOX9 targets, suggesting a role for TET1 in mediating activation of a subset of the SOX9 target genes. Using genome‐wide mapping of 5hmC during ATDC5 differentiation, we found that 5hmC is preferentially accumulated at chondrocyte‐specific class II binding sites for SOX9, as compared with the tissue‐agnostic class I sites. Specifically, we find that SOX9 is unable to bind to Col2a1 and Acan after Tet1 KD, despite no changes in SOX9 levels. Finally, we compared this KD scenario with the genetic loss of TET1 in the growth plate using Tet1−/− embryos, which are approximately 10% smaller than their WT counterparts. In E17.5 Tet1−/− embryos, loss of SOX9 target gene expression is more modest than upon Tet1 KD in vitro. Overall, our data suggest a role for TET1‐mediated 5hmC deposition in partly shaping an epigenome conducive for SOX9 function. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. |
| اللغة: | English |
| تدمد: | 2473-4039 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::fb9e2cbb2a13952ad1cda717b360cf5cTest https://hal.archives-ouvertes.fr/hal-03815584Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.dedup.wf.001..fb9e2cbb2a13952ad1cda717b360cf5c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 24734039 |
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