Figure 1.

Isolation and characterization of primate TNF-α promoters. Alignment of the consensus human TNF-α gene promoter and TNF-α promoters from seven nonhuman primate species: Pan (chimpanzee), Gorilla, Pongo (orangutan), Hylo (gibbon), Papio (baboon), Macaca (macaque), and Aotus (owl monkey), from −958 to +70 relative to the human TNF-α transcription start site. The largest continuous conserved region among all eight species is in boldface. Nucleotide positions marked by “_” represent insertion/deletion differences. We observed heterozygosity in the Macaca sequence at −445 (C/T) and at −334 (C/T), and in the Papio sequence at −294 (A/C). Sequences in GenBank report some differences from our results. A Papio sequence derived from the peripheral blood of a P. hamadryas ursinus individual contains a C at −294 and a T and −161 (GenBank accession no. AF027198) (14). A sequence in GenBank for Pongo pygmaeus assigns a G at −264 (accession no. U42764), a sequence for Pan troglodytes assigns a G at −9 (accession no. U42626), and a sequence for G. gorilla assigns a G at −9 (accession number U42763). Previously identified human SNPs are indicated (−862, −856, −375, −307, −243, −237, and +70). We note that other human SNPs have been reported (−574, −418, −162, and −48), but have been observed only in one individual (16, 21, 36). DNA-binding domains for the transcription factors nuclear factor of activated T cells (NFAT) (117-NFAT/Ets, κ3-NFAT, and −76-NFAT), ATF-2/Jun (cyclic AMP response element) Ets (−117-NFAT/Ets, −84-Ets), and Sp1 (SP-1), which are critical for TNF-α gene regulation (4–7, 12), are noted. Two NF-κB sites (κ1 and κ2) that bind NF-κB proteins in in vitro assays (9) that occur in upstream regions not essential for gene regulation are also noted.