The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Subnuclear targeting of Runx/Cbfa/AML factors is essential for tissue-specific differentiation during embryonic development
Open accessAbstract
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 (Runx2ΔC) 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 Runx2ΔC 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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Cites
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Self-citationMutations Involving the Transcription Factor CBFA1 Cause Cleidocranial Dysplasia
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Cited by
Canonical WNT Signaling Promotes Osteogenesis by Directly Stimulating Runx2 Gene Expression
Gaur, T., Lengner, C. J., Hovhannisyan, H., Bhat, R. A., Bodine, P. V. N., Komm, B. S., Javed, A., van Wijnen, A. J., Stein, J. L., Stein, G. S., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500608200 · Cited by 1,170
Self-citationZaidi, S. K., Sullivan, A. J., Medina, R., Ito, Y., van Wijnen, A. J., Stein, J. L., Lian, J. B., & Stein, G. S. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600073 · Cited by 398
Self-citationZhang, L., Jiao, G., Ren, S., Zhang, X., Li, C., Wu, W., Wang, H., Liu, H., Zhou, H., & Chen, Y. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-1562-9 · Cited by 357
Mengshol, J. A. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.21.4361 · Cited by 256
Saltman, L. H., Javed, A., Ribadeneyra, J., Hussain, S., Young, D. W., Osdoby, P., Amcheslavsky, A., van Wijnen, A. J., Stein, J. L., Stein, G. S., et al. (2005) · Journal of Cellular Physiology · doi:10.1002/jcp.20329 · Cited by 28
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Metadata
- Authors
- Choi, J.-Y., Pratap, J., Javed, A., Zaidi, S. K., Xing, L., Balint, E., Dalamangas, S., Boyce, B., van Wijnen, A. J., Lian, J. B., Stein, J. L., Jones, S. N., & Stein, G. S.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2001-07-03
- Volume
- 98
- Issue
- 15
- Pages
- 8650-8655
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2034023141
- Cited by
- 272
- References
- 55
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- green
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- Choi, J.-Y., Pratap, J., Javed, A., Zaidi, S. K., Xing, L., Balint, E., Dalamangas, S., Boyce, B., van Wijnen, A. J., Lian, J. B., Stein, J. L., Jones, S. N., & Stein, G. S. (2001). Subnuclear targeting of Runx/Cbfa/AML factors is essential for tissue-specific differentiation during embryonic development. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.151236498
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