Transcriptional regulation of the mBMP-4 gene through an E-box in the 5'-flanking promoter region involving USF

Biochem Biophys Res Commun. 1997 Nov 7;240(1):136-41. doi: 10.1006/bbrc.1997.7618.

Abstract

We analyzed the promoter activity of murine bone morphogenetic protein-4 (mBMP-4) and determined that the 5'-flanking region of exon I plays a critical role for transcription and position -265 to -246 of 5'-flanking region of mBMP-4 gene acts as a cis-element important for the regulation of BMP4 transcription in MC3T3E1 cells. By use of site-directed mutagenesis, we have established that the E-box, CACGTG, located within this short region of promoter, is essential for transcriptional activation of the mBMP-4 gene. Upstream stimulatory factor (USF), a member of the helix-loop-helix (HLH) group of regulatory proteins, was found to bind to this E-box using supershift gel mobility analysis. It is proposed that the HLH transcription regulatory proteins play an important role in mBMP-4 gene transcription in this osteoblastic cell line.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive / genetics
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins / genetics*
  • Bone Morphogenetic Proteins / metabolism
  • Cell Line
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation*
  • Helix-Loop-Helix Motifs / genetics
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Osteoblasts
  • Promoter Regions, Genetic*
  • Sequence Deletion
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Upstream Stimulatory Factors

Substances

  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Transcription Factors
  • Upstream Stimulatory Factors
  • Usf1 protein, mouse