ArticleNature communications2022
TET enzymes regulate skeletal development through increasing chromatin accessibility of RUNX2 target genes.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 63 citations in OpenAlex.
- Nrf2-Keap1 Axis Modulation by Phytofabricated Metal Oxide Nanoparticles in Mesenchymal Stem Cell Lineage Bias.Journal of biochemical and molecular toxicology · 2026Review
- Recapitulating Endochondral Ossification for Bone Repair: From Development to Engineering Strategy.Advanced healthcare materials · 2026Review
- Aberrant Kupffer-like differentiation of hematopoietic stem cell is critical for the MDS pathogenesis in Setd2-deficient mice.Cell death and differentiation · 2026Article
- SP1 recruits TET1 to mediate Kif1a demethylation and synaptic remodeling in a mouse model of chronic migraine.The journal of headache and pain · 2026Article
- Orphan Nuclear Receptor NR4A1 Promotes Proliferation and Osteogenic Differentiation of Valvular Interstitial Cells through Activation of CCND2.International journal of biological sciences · 2026Article
- Therapeutic Approaches for Enhancing Spinal Fusion in Low Back Pain: A Review With a Focus on the Elderly.JOR spine · 2025Review
- TET3-Interacting LncRNA TILR Is Essential for DNA Hydroxymethylation-Mediated Neuroprotection After Ischemic Stroke.Stroke · 2025Article
- DNA hydroxy methylases Tet1 and Tet2 regulate bone aging and bone marrow stromal cell metabolism through the IGF-1/mTOR signaling axis.Stem cells (Dayton, Ohio) · 2025Article
- Cell identity and 5-hydroxymethylcytosine.Epigenetics & chromatin · 2025Review
- Article
- Thalidomide-induced limb malformations: an update and reevaluation.Archives of toxicology · 2025Review
- Tet2 loss and enhanced ciliogenesis suppress α-synuclein pathology.Acta neuropathologica communications · 2025Article
- Recent advances of DNA methylation in osteonecrosis of the femoral head.Frontiers in genetics · 2025Review
- Antigen experience history directs distinct functional states of CD8Nature immunology · 2025Article
- Cellular stress and epigenetic regulation in adult stem cells.Life science alliance · 2024Review
- Novel peptides with calcium-binding capacity from antler bone hydrolysate, its bioactivity on MC3T3-E1 cells, and the possible chelating mode.Food science & nutrition · 2024Article
- Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis.Cell discovery · 2024Review
- Tricarboxylic Acid Cycle Regulation of Metabolic Program, Redox System, and Epigenetic Remodeling for Bone Health and Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Nucleic acid and protein methylation modification in renal diseases.Acta pharmacologica Sinica · 2024Review
- Hypermethylation of Bmp2 and Fgfr2 Promoter Regions in Bone Marrow Mesenchymal Stem Cells Leads to Bone Loss in Prematurely Aged Mice.Aging and disease · 2024Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Ten-eleven translocation (TET) family of dioxygenases mediate cytosine demethylation by catalyzing the oxidation of 5-methylcytosine (5mC). TET-mediated DNA demethylation controls the proper differentiation of embryonic stem cells and TET members display functional redundancy during early gastrulation. However, it is unclear if TET proteins have functional significance in mammalian skeletal development. Here, we report that Tet genes deficiency in mesoderm mesenchymal stem cells results in severe defects of bone development. The existence of any single Tet gene allele can support early bone formation, suggesting a functional redundancy of TET proteins. Integrative analyses of RNA-seq, Whole Genome Bisulfite Sequencing (WGBS), 5hmC-Seal and Assay for Transposase-Accessible Chromatin (ATAC-seq) demonstrate that TET-mediated demethylation increases the chromatin accessibility of target genes by RUNX2 and facilities RUNX2-regulated transcription. In addition, TET proteins interact with RUNX2 through their catalytic domain to regulate cytosine methylation around RUNX2 binding region. The catalytic domain is indispensable for TET enzymes to regulate RUNX2 transcription activity on its target genes and to regulate bone development. These results demonstrate that TET enzymes function to regulate RUNX2 activity and maintain skeletal homeostasis.
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