Binding of two nuclear complexes to a novel regulatory element within the human S100A9 promoter drives the S100A9 gene expression

J Biol Chem. 2002 Nov 1;277(44):41879-87. doi: 10.1074/jbc.M207990200. Epub 2002 Aug 7.


S100A9, also referred to as MRP14, is a calcium-binding protein whose expression is tightly regulated during differentiation of myeloid cells. The present study was performed to study the cell type- and differentiation-specific transcriptional regulation of the S100A9 gene. Analysis of the S100A9 promoter in MonoMac-6 cells revealed evidence for a novel regulatory region from position -400 to -374 bp, termed myeloid-related protein regulatory element (MRE). MRE deletion resulted in a 5.2-fold reduction of promoter activity. By electrophoretic mobility shift analysis two nuclear complexes binding to this region were identified and referred to as MRE-binding complex A (MbcA) and MRE-binding complex B (MbcB). By mutagenesis the MRE-binding motif could be narrowed to a 12-bp region. The relevance of MRE is deduced from the observations that the formation of either MRE-binding complex A or MRE-binding complex B strongly correlated with S100A9 gene expression in a cell type-specific, activation- and differentiation-dependent manner. Moreover, DNA affinity chromatography and Western blot studies indicate that a Kruppel-related zinc finger protein and the transcriptional intermediary factor 1beta (TIF1beta) are involved in an MRE-binding complex, thereby regulating the S100A9 gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Bone Marrow / metabolism
  • Calgranulin B / genetics*
  • Cell Differentiation
  • Cell Line
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / physiology
  • Gene Expression Regulation*
  • Genes, Regulator / physiology*
  • Humans
  • Molecular Sequence Data
  • Promoter Regions, Genetic*
  • Protein Binding
  • Repressor Proteins / physiology
  • Tripartite Motif-Containing Protein 28
  • Zinc Fingers / physiology


  • Calgranulin B
  • DNA-Binding Proteins
  • Repressor Proteins
  • TRIM28 protein, human
  • Tripartite Motif-Containing Protein 28