GSBS Student Publications

Title

Subnuclear targeting of Runx/Cbfa/AML factors is essential for tissue-specific differentiation during embryonic development

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cell Biology

Date

7-5-2001

Document Type

Article

Medical Subject Headings

Animals; Cell Differentiation; Cell Nucleus; Core Binding Factor Alpha 1 Subunit; Core Binding Factor alpha Subunits; Embryonic and Fetal Development; Hela Cells; Humans; Mice; Mice, Inbred C57BL; Mutagenesis; *Neoplasm Proteins; Osteogenesis; Transcription Factors; Transcription, Genetic

Disciplines

Life Sciences | Medicine and Health Sciences

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.

Rights and Permissions

Citation: Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8650-5. Epub 2001 Jul 3. Link to article on publisher's site

DOI of Published Version

10.1073/pnas.151236498

Related Resources

Link to article in PubMed

Journal Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID

11438701