Authors
Je-Yong Choi, Jitesh Pratap, Amjad Javed, S Kaleem Zaidi, Lianping Xing, Eva Balint, Sara Dalamangas, Brendan Boyce, Andre J Van Wijnen, Jane B Lian, Janet L Stein, Stephen N Jones, Gary S Stein
Publication date
2001/7/17
Journal
Proceedings of the National Academy of Sciences
Volume
98
Issue
15
Pages
8650-8655
Publisher
National Acad Sciences
Description
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 …
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Scholar articles
JY Choi, J Pratap, A Javed, SK Zaidi, L Xing, E Balint… - Proceedings of the National Academy of Sciences, 2001