Subnuclear targeting of Runx/Cbfa/AML factors is essential for tissue-specific differentiation during embryonic development
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- Je-Yong Choi
- Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655; and Department of Pathology, University of Rochester Medical School, 601 Elmwood Avenue, Box 626, Rochester, NY 14642
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- Jitesh Pratap
- Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655; and Department of Pathology, University of Rochester Medical School, 601 Elmwood Avenue, Box 626, Rochester, NY 14642
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- Amjad Javed
- Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655; and Department of Pathology, University of Rochester Medical School, 601 Elmwood Avenue, Box 626, Rochester, NY 14642
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- S. Kaleem Zaidi
- Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655; and Department of Pathology, University of Rochester Medical School, 601 Elmwood Avenue, Box 626, Rochester, NY 14642
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- Lianping Xing
- Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655; and Department of Pathology, University of Rochester Medical School, 601 Elmwood Avenue, Box 626, Rochester, NY 14642
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- Eva Balint
- Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655; and Department of Pathology, University of Rochester Medical School, 601 Elmwood Avenue, Box 626, Rochester, NY 14642
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- Sara Dalamangas
- Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655; and Department of Pathology, University of Rochester Medical School, 601 Elmwood Avenue, Box 626, Rochester, NY 14642
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- Brendan Boyce
- Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655; and Department of Pathology, University of Rochester Medical School, 601 Elmwood Avenue, Box 626, Rochester, NY 14642
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- André J. van Wijnen
- Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655; and Department of Pathology, University of Rochester Medical School, 601 Elmwood Avenue, Box 626, Rochester, NY 14642
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- Jane B. Lian
- Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655; and Department of Pathology, University of Rochester Medical School, 601 Elmwood Avenue, Box 626, Rochester, NY 14642
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- Janet L. Stein
- Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655; and Department of Pathology, University of Rochester Medical School, 601 Elmwood Avenue, Box 626, Rochester, NY 14642
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- Stephen N. Jones
- Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655; and Department of Pathology, University of Rochester Medical School, 601 Elmwood Avenue, Box 626, Rochester, NY 14642
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- Gary S. Stein
- Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655; and Department of Pathology, University of Rochester Medical School, 601 Elmwood Avenue, Box 626, Rochester, NY 14642
説明
<jats:p>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.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 98 (15), 8650-8655, 2001-07-03
Proceedings of the National Academy of Sciences