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

Lookup NU author(s): Professor Hermann Josef Vormoor

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Abstract

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 metadata

Author(s): Kerkhoff C, Hofmann HA, Vormoor J, Melkonyan H, Roth J, Sorg C, Klempt M

Publication type: Article

Publication status: Published

Journal: Journal of Biological Chemistry

Year: 2002

Volume: 277

Issue: 44

Pages: 41879-41887

ISSN (print): 0021-9258

ISSN (electronic): 1083-351X

URL: http://dx.doi.org/10.1074/jbc.M207990200

DOI: 10.1074/jbc.M207990200

Notes: 0021-9258 (Print) Journal Article


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