Cloning and characterization of human complement component C7 promoter

Abstract

To study the transcriptional regulation of the human complement component C7, a 1 kb promoter fragment was cloned and the transcription start site was determined. C7 is expressed by the hepatoma-derived cell line Hep-3B, but not by Hep-G2. Transfection of these cell lines with different C7 promoter-luciferase constructs demonstrated that 1 kb of the 5 0 -flanking region contains the necessary elements for driving C7 transcription in a tissue-specific manner and showed that the sequence between À29/+102 retained the majority of C7 promoter activity in Hep-3B. Electrophoretic mobility shift assays suggested that the binding of the C/EBPa transcription factor to a C/EBP sequence located at +42 is essential for C7 expression. To investigate whether the absence of C/EBPa expression in Hep-G2 cells is responsible for the lack of C7 transcription, Hep-G2 cells were transfected with a C/EBPa expression vector. C/EBPa transactivated the C7 luciferase reported gene and restored the C7 expression in Hep-G2 cells.

Hepatocytes: a key cell type for innate immunity

“…In normal and healthy liver, C/EBP-α and C/EBP-ζ are the two predominant forms of C/EBPs in hepatocytes. C/EBP-α controls the basal expression level of many innate immunity proteins in hepatocytes, including complement component C3, 131 C6, 132 C7, 133 SAA, 134 and fibrinogen β. 135 The critical role of C/EBP-α is supported by the fact that C/EBP-α-knockout mice are almost completely resistant to LPS- or IL-1β-mediated induction of APPs in the liver.…”

Polymorphic sites in the 5´-region of the porcine <i>C8A</i> gene

“…Most of the transcription factor binding site motifs analyzed in the 5´-region of the porcine C8A have previously been identified in other complement components such as the human C3 (Vik et al 1991), human C6 (González & López-Larrea 1996), human C7 (González et al 2003), murine C5 (Haviland et al 1991) or grass carp C9 (Li et al 2007). In particular, C/EBPs are basic region leucine zipper transcription factors that regulate cell differentiation, growth, survival, and inflammation (Miller et al 2003).…”

“…In particular, C/EBPs are basic region leucine zipper transcription factors that regulate cell differentiation, growth, survival, and inflammation (Miller et al 2003). Therefore, C/EBP is essential for the human C6 and C7 expression (González & López-Larrea 1996, González et al 2003. C/EBP delta is also the major protein responsible for regulating the acute-phase expression of the human C3 gene (Juan et al 1993).…”