Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Kerkhoff, C. et al.

Kerkhoff, Hofmann, Vormoor, Melkonyan, Roth, Sorg, Klempt,

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

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.[1]

References

Binding of two nuclear complexes to a novel regulatory element within the human S100A9 promoter drives the S100A9 gene expression. Kerkhoff, C., Hofmann, H.A., Vormoor, J., Melkonyan, H., Roth, J., Sorg, C., Klempt, M. J. Biol. Chem. (2002) [Pubmed]

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