A specific targeting signal directs Runx2/Cbfa1 to subnuclear domains and contributes to transactivation of the osteocalcin gene

S. K. Zaidi, A. Javed, J. Y. Choi, A. J. Van Wijnen, J. L. Stein, J. B. Lian, G. S. Stein

Research output: Contribution to journalArticle

141 Scopus citations

Abstract

Key components of DNA replication and the basal transcriptional machinery as well as several tissue-specific transcription factors are compartmentalized in specialized nuclear domains. In the present study, we show that determinants of subnuclear targeting of the bone-related Runx2/Cbfa1 protein reside in the C-terminus. With a panel of C-terminal mutations, we further demonstrate that targeting of Runx2 to discrete subnuclear foci is mediated by a 38 amino acid sequence (aa 397-434). This nuclear matrix-targeting signal (NMTS) directs the heterologous Gal4 protein to nuclear-matrix-associated Runx2 foci and enhances transactivation of a luciferase gene controlled by Gal4 binding sites. Importantly, we show that targeting of Runx2 to the NM-associated foci contributes to transactivation of the osteoblast-specific osteocalcin gene in osseous cells. Taken together, these findings identify a critical component of the mechanisms mediating Runx2 targeting to subnuclear foci and provide functional linkage between subnuclear organization of Runx2 and bone-specific transcriptional control.

Original languageEnglish (US)
Pages (from-to)3093-3102
Number of pages10
JournalJournal of cell science
Volume114
Issue number17
StatePublished - Oct 10 2001

Keywords

  • Nuclear localization
  • Nuclear matrix
  • Osteoblasts
  • Osteocalcin
  • Transcriptional control

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'A specific targeting signal directs Runx2/Cbfa1 to subnuclear domains and contributes to transactivation of the osteocalcin gene'. Together they form a unique fingerprint.

  • Cite this

    Zaidi, S. K., Javed, A., Choi, J. Y., Van Wijnen, A. J., Stein, J. L., Lian, J. B., & Stein, G. S. (2001). A specific targeting signal directs Runx2/Cbfa1 to subnuclear domains and contributes to transactivation of the osteocalcin gene. Journal of cell science, 114(17), 3093-3102.