A MEMBER OF THE C/EBP FAMILY, NF-IL6-BETA, FORMS A HETERODIMER AND TRANSCRIPTIONALLY SYNERGIZES WITH NF-IL6

Using a DNA probe from the DNA-binding portion of the NF-IL6 gene and an antibody against the DNA-binding domain of NF-IL6, we isolated a gene homologous to NF-IL6 in the DNA-binding and leucine zipper domains. This intronless gene, termed NF-IL6-beta encodes a 269-amino acid protein with a Potential leucine zipper structure, and the gene product can bind to the CCAAT homology as well as the viral enhancer core sequence, as in the cases of NF-IL6 and C/EBP. This gene is expressed at an undetectable or a minor level in normal tissues but is induced by lipopolysaccharide or inflammatory cytokines, as in the case of NF-IL6. NF-IL6-beta easily forms a heterodimer with NF-IL6 in vitro and the heterodimeric complex binds to the same DNA sequence as the respective homodimers. When examined by transient luciferase assays, NF-IL6-beta is consistently a stronger trans-activator than NF-IL6. Furthermore, NF-IL6-beta shows a synergistic transcriptional effect with NF-IL6. These data suggest that NF-IL6-beta is an important transcriptional activator in addition to NF-IL6 in regulation of the genes involved in the immune and inflammatory responses.