The Basic Amino Acid-Rich DNA-Binding Element of the NF-IL6 Transcription Factor Contains Two Functionally Distinct Subdomains.

: Nuclear factor-interleukin-6 (NF-IL6), a human transcription factor of the CCAAT-box/enhancer binding protein (C/EBP) family, is widely implicated as a "master regulator" of hepatic acute-phrase response and inflammatory cytokine gene expression. NF-IL6 contains, at its N-terminus, an alanine- and proline-rich transactivation domain, followed at the C-terminus by a basic domain-leucine zipper (bZIP) DNA-binding motif. Understanding how the NF-IL6 transcription factor interacts with DNA is fundamental to its role as a transactivator because sequence-specific DNA-binding is prerequisite to promoter activation. We review our findings on the identification of the minimal "core" DNA-binding domain and the discovery of a novel bZIP element that influences DNA-binding kinetics. Manipulation of this domain allows for design of molecules that can be used as competitive antagonists or targeted delivery of molecules to selected regions of the eukaryotic genome.