Binding of Two Nuclear Complexes to a Novel Regulatory Element within the Human S100A9 Promoter Drives the S100A9 Gene Expression

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 differentiationspecific 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 differentiationdependent manner. Moreover, DNA affinity chromatography and Western blot studies indicate that a Kruppelrelated zinc finger protein and the transcriptional intermediary factor 1␤ (TIF1␤) are involved in an MREbinding complex, thereby regulating the S100A9 gene expression.

Mechanism of apoptosis induced by S100A8/A9 in colon cancer cell lines: the role of ROS and the effect of metal ions

“…[13,14]). The expression of the two S100 proteins is restricted to a specific stage of myeloid differentiation, probably driven by a recently characterized regulatory element [15]. In addition to the binding to Ca 2ϩ , S100A8/A9 has been shown to bind other bivalent cations, such as Zn 2ϩ and Cu 2ϩ [4, 16 -19].…”

Bilateral induction of the S-100A9 gene in response to spreading depression is modulated by the cyclooxygenase-2 activity

“…The S-100A8/A9 complex was reported to specifically bind to polyunsaturated fatty acids in a calcium-dependent manner [31,32], and it has been implicated in the modulation of the activity of arachidonic acid-metabolizing enzymes [33]. Neuronal activity during SD that is mediated by the NMDA receptor could help propagate astrocytic calcium waves into the brain areas contralateral to the affected side [34 -36].…”

Involvement of Nrf2 activation in the upregulation of S100A9 by exposure to inorganic arsenite

“…The expression of S100A8 and S100A9 genes could be regulated in either harmonized or independent ways. Some studies have suggested a more important role of S100A9 than S100A8 (17,18), and cis-elements for trans-activation on the human S100A9 gene have been well documented (19,20). Thus, we focused on the mechanisms underlying S100A9 trans-activation in HaCaT cells exposed to As(III).…”

“…A study with human mature monocytic Mono Mac 6 cells, which exhibit high S100A9 expression under steady-state conditions (20), showed that expression of S100A9 was dependent on the two regions in the promoter of the S100A9 gene, from 153 to 361 (first intron) and from -400 to -374 (promoter region). Additionally, the Kruppel-related zinc finger protein and the transcriptional intermediary factor 1β (TIF1β) were shown to bind to the region from -400 to -374 in the promoter of the S100A9 gene, resulting in the upregulation of S100A9 expression (19,20). Further studies are required to clarify whether the Kruppel-related zinc finger protein and TIF1β are activated by As(III) in HaCaT cells.…”