Regulation of NF-κB by Its Binding Site

Abstract

We often think of DNA binding sites as dictating the particular transcription factor that will bind and in that way determining how transcription is regulated. However, evidence is accumulating that the interaction provides additional information and may actually allosterically modify the bound transcription factor. Leung et al. noted unusual conservation of binding sites for the transcription factor NF-κB in human and mouse genes and therefore tested the effects of single nucleotide changes on gene regulation at such a site. In mouse 3T3 cells infected with lentivirus that permitted modification of the endogenous gene promoter, a single nucleotide change was found to have no effect on binding of the transcription factor, but rather to alter the requirement for a particular coactivator, IRF3. The authors suggest that conformational changes in the bound NF-κB molecule likely account for altered preference for cofactors when bound to different promoters. T. H. Leung, A. Hoffmann, D. Baltimore, One nucleotide in a κB site can determine cofactor specificity for NF-κB dimers. Cell 118 , 453-464 (2004). [Online Journal]