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

Academic Article

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.
  • Published In

    Keywords

  • Amino Acid Sequence, Animals, Binding Sites, Blotting, Western, Cell Nucleus, Core Binding Factor Alpha 1 Subunit, DNA-Binding Proteins, Fungal Proteins, Genes, Reporter, HeLa Cells, Humans, In Situ Hybridization, Luciferases, Microscopy, Fluorescence, Molecular Sequence Data, Mutation, Neoplasm Proteins, Osteocalcin, Plasmids, Protein Structure, Tertiary, Rats, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid, Signal Transduction, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Tumor Cells, Cultured
  • Digital Object Identifier (doi)

    Author List

  • Zaidi SK; Javed A; Choi JY; van Wijnen AJ; Stein JL; Lian JB; Stein GS
  • Start Page

  • 3093
  • End Page

  • 3102
  • Volume

  • 114
  • Issue

  • Pt 17