Characterization of the 5′ Flanking Region of the Human Complement Factor H Gene

Abstract

Williams SA, Vik DP. Characterization of the 5 0 Flanking Region of the Human Complement Factor H Gene. Scand J Immunol 1997;45:7-15 The promoter region of the human factor H gene was cloned and a 3 kb Eco RI fragment was sequenced. Primer extension and S1 nuclease analysis were used to determine the transcription start site, which was found to be 10-11 nucleotides upstream of the published cDNA sequence. No canonical TATA or CCAAT boxes were found in conjunction with this site. The sequence from the human H promoter region was compared to that from the mouse gene. There was a region of 800 bp that was 62.5% identical between the two sequences. The sequences of the two promoter regions were compared to a database of transcription factor binding sites. Five elements were identified that matched the consensus sequence 100% and were identical in the two promoter sequences. Promoter assays using the luciferase reporter gene demonstrated that this region contained a functional transcription start site and putative enhancer elements. U118-MG astroglioma cells and Hep3b hepatoma cells were incubated with various cytokines to measure effects on their factor H mRNA levels. Interferon-(IFN-), but not interleukin-1 (IL-1), tumour necrosis factor (TNF-) or IL-6, was able to increase the level of H mRNA in both cell lines.

Complement factor H gene (CFH) polymorphisms C-257T, G257A and haplotypes are associated with protection against severe dengue phenotype, possible related with high CFH expression

“…CFH gene (1q32, locus ID: 3075) encodes for the CFH . The CFH promoter was characterized by Willians et al [26] and the conserved transcription starting sites were described. To date, the single nucleotide polymorphism (SNP) NCBI database reported some SNPs located within the promoter and CFH gene [25].…”

Interleukin 27 Induces the Expression of Complement Factor H (CFH) in the Retina

“…Significant amounts of CFH are also produced in the eye, with the highest levels detected in the retinal pigment epithelia (RPE), choroid and the retina [13]. The pro-inflammatory cytokine, IFN-g has been shown to up-regulate the expression of CFH in hepatocytes, astrocytes, lung cells and astroglioma cell lines [14], [15] and these observations are consistent with the presence of two IFN-g activation sites (GAS) within the CFH proximal promoter [16], [17], [18]. With the knowledge that defects in CFH production may contribute to the development of AMD, it is remarkable that less is known about mechanisms involved in the regulation of CFH production in the normal retina.…”

c-Jun and c-Fos regulate the complement factor H promoter in murine astrocytes

“…Despite the fact that TNF-α, IL-6, IL-lβ and IFN-γ have all been implicated in CFH expression (Julen et al, 1992; Klein et al, 2005), our finding that IFN-γ is the one cytokine of the four to make an impact on CFH production in murine astrocytes is established in the literature for other cell types, such as hepatocytes, lung cells and human astroglioma cell lines (Gasque et al, 1995; Gasque et al, 1992; Williams and Vik, 1997). These data correspond to two IFN-γ activation sites (GAS), TTCNNGAA and TTNCNNNAA (Darnell et al, 1994) located at positions −237 to −228 and positions −194 to −185 within the m CFH promoter.…”

“…The transcription start site of the CFH promoter had been documented decades ago utilizing the RNAse protection and S1 nuclease assays to determine the CFH start of transcription (Munoz-Canoves et al, 1989; Williams and Vik, 1997). Our analysis using the SMARTer RACE kit technology indicates an alternate start site in astrocytes and microglia, as well as in liver tissue.…”

“…Astrocytes do not respond to IL-6 well and not every astrocyte has the IL-6 receptor subunit gp130 (Van Wagoner and Benveniste, 1999), and this might be due to the fact that IL-6 needs to be administered with nerve growth factor to elicit a response (Jauneau et al, 2006). TNF-α has been thought to have no affect (Friese et al, 1999) or decrease CFH mRNA production that had been previously stimulated by IFN-γ (Williams and Vik, 1997). Additionally, in RPE cells, TNF-α and IL-6 were thought to downregulate CFH expression (Chen et al, 2007; Kim et al, 2009), indicating that TNF-α likely has a negative effect on CFH regulation but requires other cytokines.…”