Structural features of the human C3 gene: Intron/exon organization, transcriptional start site, and promoter region sequence

Department of Pediatrics, Washington University in St. Louis, San Luis, Missouri, United States
Biochemistry (Impact Factor: 3.02). 02/1991; 30(4):1080-5. DOI: 10.1021/bi00218a029
Source: PubMed


The third component of human complement (C3) is a key molecule in the activation of the complement cascade. C3 cDNA fragments were used to identify seven cosmid clones that covered all but 1 kilobase pair (kb) of the C3 gene. The remainder of the gene was cloned by using the polymerase chain reaction. These clones were used to identify the intron/exon boundaries and to map the gene. The C3 gene is 42 kb in length and comprises 41 exons ranging in size from 52 to 213 base pairs (bp). The transcription start site was identified by primer extension, and approximately 1 kb of DNA upstream of this site was sequenced. Putative TATA and CAAT boxes were identified along with a number of regions that shared homology with known regulatory sequences. These include responsive elements for interferon-gamma, interleukin-6, nuclear factor kappa B, estrogen, glucocorticoids and thyroid hormone. Several of these agents have been shown to affect C3 synthesis and mRNA levels. The sizes of the exons in C3 were compared to those of C4 and alpha 2-macroglobulin (alpha 2M). Thirty-nine of 41 exons in C4 were found to be of similar size to the analogous ones in C3, and two-thirds of those in alpha 2M were also similarly sized, supporting the hypothesis that these genes arose from a common ancestor.

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    • "In the aging female cortex, we demonstrated down-regulation of C3 in the presence of estrogens. This finding is in line with the presence of 3 ERE sequences in the C3 promoter [57,58] and estrogenic regulation of C3 in other tissues [59]. Up-regulation of early C components has been reported recently in the aging mouse forebrain [60]. "
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    Journal of Neuroinflammation 07/2011; 8(1):82. DOI:10.1186/1742-2094-8-82 · 5.41 Impact Factor
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    • "As far as complement is concerned, the dual role of adipose tissue (metabolism and host defense) is echoed by the dual role complement plays in relation to adipose tissue: on the one hand local complement production provides a constituent of triglyceride synthesis, on the other hand it furnishes a local immune repertoire that can be activated during local and systemic inflammation. This dualism may be mirrored in the gene of the central complement component, C3, an acute phase reactant: The promoter of the C3 gene harbours estrogen-response elements (Vik et al., 1991). While there is no obvious reason why the abundance of the innate immune response should differ between the sexes, the presence of these regulatory elements may indeed more readily connect to sex-related fat metabolism. "
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    Molecular Immunology 11/2008; 46(5):755-60. DOI:10.1016/j.molimm.2008.09.013 · 2.97 Impact Factor
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    • " gene (Vik et al. 1991). The signal cascades involved are still unknown and may vary for different genes with similar sensitivity to estrogenic compounds. "
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