A human nuclear-localized chaperone that regulates dimerization, DNA binding, and transcriptional activity of bZIP proteins

We have identified and cloned a human nuclear protein that dramatically inc reases DNA binding of transcription factors that contain a basic region-leu cine zipper (bZIP) DNA binding domain. We show that this bZIP enhancing fac tor (BEF) functions as a molecular chaperone. BEF stimulates DNA binding by recognizing the unfolded leucine zipper and promoting the folding of bZIP monomers to dimers; the elevated concentration of the bZIP dimer then drive s the DNA binding reaction. Antisense experiments indicate that BEF is requ ired for efficient transcriptional activation by bZIP proteins in vivo. Our results reveal protein folding in the nucleus as a step at which sequence- specific DNA binding proteins can be regulated.