ArticleProceedings of the National Academy of Sciences of the United States of America2001
Subnuclear targeting of Runx/Cbfa/AML factors is essential for tissue-specific differentiation during embryonic development.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
127 citing papers in PubMed, 271 citations in OpenAlex.
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- Peptidylarginine deiminase 2 plays a key role in osteogenesis by enhancing RUNX2 stability through citrullination.Cell death & disease · 2023Article
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- Similarities Between Disuse and Age-Induced Bone Loss.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Review
- Identification of a familial cleidocranial dysplasia with a novel RUNX2 mutation and establishment of patient-derived induced pluripotent stem cells.Odontology · 2022Article
- Construction of tissue-engineered nucleus pulposus by stimulation with periodic mechanical stress and BMP-2.iScience · 2022Article
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- SATB2: A versatile transcriptional regulator of craniofacial and skeleton development, neurogenesis and tumorigenesis, and its applications in regenerative medicine.Genes & diseases · 2022Review
- Runx2 is required for hypertrophic chondrocyte mediated degradation of cartilage matrix during endochondral ossification.Matrix biology plus · 2021Article
- Genome-scale actions of master regulators directing skeletal development.The Japanese dental science review · 2021Review
- Hypoxia-inducible factor 2α is a novel inhibitor of chondrocyte maturation.Journal of cellular physiology · 2021Article
- Two Novel C-Terminus RUNX2 Mutations in Two Cleidocranial Dysplasia (CCD) Patients Impairing p53 Expression.International journal of molecular sciences · 2021Article
- Osteogenic differentiation cues of the bone morphogenetic protein-9 (BMP-9) and its recent advances in bone tissue regeneration.Materials science & engineering. C, Materials for biological applications · 2021Review
- TLE4 Is a Critical Mediator of Osteoblast and Runx2-Dependent Bone Development.Frontiers in cell and developmental biology · 2021Article
- Runx Transcription Factors in T Cells-What Is Beyond Thymic Development?Frontiers in immunology · 2021Review
- Transcriptional Programming in Arteriosclerotic Disease: A Multifaceted Function of the Runx2 (Runt-Related Transcription Factor 2).Arteriosclerosis, thrombosis, and vascular biology · 2021Review
- Article
67 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Runx (Cbfa/AML) transcription factors are critical for tissue-specific gene expression. A unique targeting signal in the C terminus directs Runx factors to discrete foci within the nucleus. Using Runx2/CBFA1/AML3 and its essential role in osteogenesis as a model, we investigated the fundamental importance of fidelity of subnuclear localization for tissue differentiating activity by deleting the intranuclear targeting signal via homologous recombination. Mice homozygous for the deletion (Runx2 Delta C) do not form bone due to maturational arrest of osteoblasts. Heterozygotes do not develop clavicles, but are otherwise normal. These phenotypes are indistinguishable from those of the homozygous and heterozygous null mutants, indicating that the intranuclear targeting signal is a critical determinant for function. The expressed truncated Runx2 Delta C protein enters the nucleus and retains normal DNA binding activity, but shows complete loss of intranuclear targeting. These results demonstrate that the multifunctional N-terminal region of the Runx2 protein is not sufficient for biological activity. We conclude that subnuclear localization of Runx factors in specific foci together with associated regulatory functions is essential for control of Runx-dependent genes involved in tissue differentiation during embryonic development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.