The complete exon-intron structure of the 156-kb human gene NFKB1, which encodes the p105 and p50 proteins of transcription factors NF-kappa B and I kappa B-gamma: implications for NF-kappa B-mediated signal transduction.

The NFKB1 gene encodes three proteins of the NF-kappa B/Rel and I kappa B families: p105, p50, and (in mouse) I kappa B-gamma. We determined the complete genomic structure of human NFKB1. NFKB1 spans 156 kb and has 24 exons with introns varying between 40,000 and 323 bp in length. Although NFKB2, which encodes p100 and p52, also has 24 exons and has a comparable exon-intron structure, it is 20 times shorter (8 kb; Fracchiola et al. (1993) Oncogene 8, 2839-2845) than NFKB1. We propose that the long size of NFKB1 is important for transient activation of NF-kappa B complexes containing p50. I kappa B-gamma corresponds to the carboxyl-terminal half of p105. DNA sequence analysis showed that the 3'-end of human intron 11 and the 5'-end of exon 12 of NFKB1 are colinear with the 5'-untranslated region of mouse I kappa B-gamma cDNA. I kappa B-gamma is thus likely to be generated by transcription starting within intron 11 and not by alternative splicing of the mouse mRNA encoding p105 and p50.