C/EBPβ binds the P1 promoter of the Runx2 gene and up-regulates Runx2 transcription in osteoblastic cells

J Cell Physiol. 2011 Nov;226(11):3043-52. doi: 10.1002/jcp.22652.

Abstract

The Runx2 factor is an essential component of the regulatory mechanisms that control transcription during skeletogenesis. Runx2/p57 expression in osteoblastic cells is controlled by the P1 promoter, which is recognized by key regulators of osteoblast differentiation including homeodomain factors and Wnt- and BMP-signaling mediators. Here, we report that the transcription factor C/EBPβ up-regulates Runx2/p57 expression by directly binding to the Runx2 P1 promoter in mesenchymal, pre-osteoblastic, and osteoblastic cells. This C/EBPβ-mediated up-regulation is principally dependent on C/EBP site II that is located within the first 180 bp of the proximal P1 promoter region and is highly conserved among mouse, rat, and human Runx2 genes. Our studies reveal how the C/EBPβ factor, known to have a key role during osteogenesis, contributes to regulating the expression of Runx2, the master regulator of osteoblast differentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • CCAAT-Enhancer-Binding Protein-beta / metabolism*
  • Cell Line
  • Core Binding Factor Alpha 1 Subunit / genetics*
  • Gene Expression Regulation*
  • Humans
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Molecular Sequence Data
  • Osteoblasts / metabolism*
  • Promoter Regions, Genetic*
  • Rats
  • Transcription, Genetic*
  • Up-Regulation

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • Core Binding Factor Alpha 1 Subunit